In The News - Press Releases

Oncotarget: Oncogene inactivation-induced apoptosis in acute lymphoblastic leukemia


Here is the link to an interview with Dr. Felsher about this research on the Oncotarget YouTube Channel

Oncotarget published "BIM mediates oncogene inactivation-induced apoptosis in multiple transgenic mouse models of acute lymphoblastic leukemia" which reported BIM mediates oncogene inactivation-induced apoptosis in multiple transgenic mouse models of acute lymphoblastic leukemia

Dr. Dean W. Felsher from Stanford University, and Founding Editorial Board member of Oncotarget said, "Although... continue reading >>

Oncotarget: Cis-acting elements in 3′ UTR mediate post-transcriptional regulation of KRAS


Here is a link to an interview with Dr. Frank Slack about this Research on the Oncotarget YouTube Channel

Oncotarget published "Cis-acting elements in its 3′ UTR mediate post-transcriptional regulation of KRAS" which reported that the KRAS gene encodes a key signaling protein, and its messenger RNA contains an exceptionally long 3′ UTR; this suggests that it may be subject to a highly complex set of regulatory processes.

Using extensive deletion and mutational analyses combined with... continue reading >>

Oncotarget: A procaspase-3 activator and temozolomide extends survival in glioma models


Here is a link to a video interview with Dr. Gregory J. Riggins about this Research on the Oncotarget YouTube Channel

Oncotarget published "Synergistic and targeted therapy with a procaspase-3 activator and temozolomide extends survival in glioma rodent models and is feasible for the treatment of canine malignant glioma patients" which studied if PAC-1 could enhance the activity of TMZ, and whether addition of PAC-1 to standard treatment would be feasible in spontaneous canine malignant... continue reading >>

Oncotarget: Significant differences in biomarker expression in pancreatic cancer


Here is a link to a video interview with Dr. Jonathan A. Kelber about this research on the Oncotarget YouTube Channel

Oncotarget published "A novel method for RNA extraction from FFPE samples reveals significant differences in biomarker expression between orthotopic and subcutaneous pancreatic cancer patient-derived xenografts" which reported that performing NGS on FFPE samples is limited by poor RNA purification methods.

To address this hurdle, the researchers developed an improved... continue reading >>

Oncotarget: Metabolic reprogramming of glioblastoma cells sensitizes for apoptosis


Here is a link to a video interview with Dr. Markus D. Siegelin & Dr. Georg Karpel-Massler about this research on the Oncotarget YouTube Channel

Oncotarget published "Metabolic reprogramming of glioblastoma cells by L-asparaginase sensitizes for apoptosis in vitro and in vivo" which reported that the results suggest that certain glioma cell cultures are particularly susceptible to inhibition of proliferation by L-asparaginase, while others display a more resistant phenotype.

In sensitive... continue reading >>

Oncotarget: Targeting mesothelin with high cytotoxic activity


Here is a link to a video interview with Dr. Ira Pastan about this research on the Oncotarget YouTube Channel

Oncotarget published "Dual B- and T-cell de-immunization of recombinant immunotoxin targeting mesothelin with high cytotoxic activity" which reported that Recombinant immunotoxins are genetically engineered proteins being developed to treat cancer.

They are composed of an Fv that targets a cancer antigen and a portion of a protein toxin.

Starting with an immunotoxin that has B-cell... continue reading >>

Oncotarget: PRG3 induces Ras-dependent oncogenic cooperation in gliomas


Here is a link to a video interview with Dr. Nicolai E. Savaskan about this research on the Oncotarget YouTube Channel

Oncotarget published "PRG3 induces Ras-dependent oncogenic cooperation in gliomas" which reported on the neuronal-associated growth promoting gene PRG3 executing oncogenic cooperation in gliomas.

The researchers have identified perturbed PRG3 levels in human malignant brain tumors displaying either elevated or down-regulated PRG3 levels compared to non-transformed specimens.

... continue reading >>

Oncotarget: Cytogenetic and molecular landscape in Hispanic CMML patients from Puerto Rico


Oncotarget recently published "Cytogenetic and molecular landscape and its potential clinical significance in Hispanic CMML patients from Puerto Rico" which reported that one hundred and eleven Hispanic CMML patients from Puerto Rico were diagnosed in their institute from 2009 to 2018.

Karyotypes were available in one hundred and seven patients.

Compared to previously published data, Hispanic CMML patients in this study had significantly lower rates of overall cytogenetic abnormalities and... continue reading >>

Oncotarget: Effect of liver fibrosis on survival in patients with intrahepatic cholangiocarcinoma


Oncotarget recently published "Effect of liver fibrosis on survival in patients with intrahepatic cholangiocarcinoma: a SEER population-based study" which reported that the impact of fibrosis on overall and cancer-specific survival 12, 36, and 60 months following diagnosis, was evaluated in the entire cohort and in subgroups stratified according to treatment approach and the American Joint Committee on Cancer tumor stage using a Cox proportional-hazards model.

After adjusting for age, sex,... continue reading >>

Oncotarget: Triptolide-induced apoptosis in non-small cell lung cancer


Oncotarget recently published "Triptolide-induced apoptosis in non-small cell lung cancer via a novel miR204-5p/Caveolin-1/Akt-mediated pathway" which reported that Lung cancer is one of the most prevalent malignancies worldwide with non-small cell lung cancer comprising nearly 80% of all cases.

Unfortunately, many lung cancer patients are diagnosed at advanced stages of the disease with an associated poor prognosis.

The authors demonstrate that triptolide treatment of A549 and H460 NSCLC... continue reading >>

Oncotarget: Can Denosumab be used in combination with Doxorubicin in Osteosarcoma?


Oncotarget recently published "Can Denosumab be used in combination with Doxorubicin in Osteosarcoma?" which reported that Denosumab is a monoclonal antibody with high affinity and specificity to RANK-L, the ligand released by osteoblasts that enhances osteoclasts differentiation and bone resorption.

The authors investigated the effects of Denosumab alone and in combination with Doxorubicin, in two human osteosarcoma cell lines.

They observed for the first time an anti-invasive effect of... continue reading >>

Oncotarget: Determination of HER oncogene co-amplifications in breast cancer


Oncotarget recently published "Working together for the family: determination of HER oncogene co-amplifications in breast cancer" which reported that despite specific treatment, unfortunately, 20% of primary and 70% of metastatic HER2 tumors develop resistance.

In addition, the authors developed a protocol based on the combination of MLPA with ddPCR to detect the tumor proportion of co-amplified HERs.

On 111 IDC, the HER2 MLPA results were validated by FISH, CISH, and IHC.

The percentage of... continue reading >>

Oncotarget: Diabetes mellitus is associated with liver metastasis of colorectal cancer


Oncotarget recently published "Diabetes mellitus is associated with liver metastasis of colorectal cancer through production of biglycan-rich cancer stroma" which reported that In this study, the authors investigated the relationship between the presence of diabetes mellitus and the progression and liver metastasis of CRC.

Histopathological findings in the primary lesions, which were preferential to diabetes-complicated CRC and the liver metastasis, were also investigated.

Histopathological... continue reading >>

Oncotarget: Ewing sarcoma family potential clinical biomarkers


Oncotarget recently published "Ewing sarcoma family of tumors-derived small extracellular vesicle proteomics identify potential clinical biomarkers" which reported that outside of tumor biopsy, no clinically relevant ESFT biomarkers exist.

Additionally, tumor burden assessment at diagnosis, monitoring of disease responsiveness to therapy, and detection of disease recurrence are limited to radiographic imaging.

To identify new, clinically relevant biomarkers the authors evaluated the proteome... continue reading >>

Mitochondrial uncoupling & metabolic network disruption in hepatocellular carcinoma


Oncotarget recently published "Mitochondrial uncoupling and the disruption of the metabolic network in hepatocellular carcinoma" which reported that the authors studied the anti-HCC effect of FH535 and a novel derivative Y3, on proliferation, mitochondrial function, and cellular metabolism focusing on the three key substrates, glutamine, glucose, and fatty acids.

FH535 and Y3 disrupted mitochondrial redox control in HCC cells that resulted from uncoupling mechanisms that increased proton... continue reading >>

Oncotarget: PD-1/PD-L1 expression in anal squamous intraepithelial lesions


Oncotarget recently published "PD-1/PD-L1 expression in anal squamous intraepithelial lesions" which reported that the presence and distribution of CD8 lymphocytes and the presence of PD-1 lymphocytes and PD-L1 epithelial cells were assessed.

CD8 lymphocytes were observed more frequently in HSIL versus LSIL in the lamina propria or intra epithelial.

PD-1 lymphocytes were observed more frequently in HSIL versus LSIL.

There was no difference between HSIL and LSIL for PD-L1 epithelial cells.

An... continue reading >>

Oncotarget: TAF15 contributes to the radiation-inducible stress response in cancer


Oncotarget recently published "ETAF15 contributes to the radiation-inducible stress response in cancer" which reported that genetically silenced TAF15 which led to a significant reduction in proliferation of NSCLC cells.

Cells depleted of TAF15 exhibited cell cycle arrest and enhanced apoptosis through activation and accumulation of p53. In combination with radiation, TAF15 knockdown led to a significant reduction in the surviving fraction of NSCLC cell lines.

To determine the importance of... continue reading >>

Oncotarget: Prognostic value of biomarkers in patients with gastric cancer


Oncotarget recently published "Comparison of the prognostic value of immunoinflammation-based biomarkers in patients with gastric cancer" which reported that in this study, the authors clarified the prognostic impact of immuno inflammation-based indices, i. e. SII, neutrophil/lymphocyte ratio, and platelet/lymphocyte ratio, in gastric cancer patients.

In multivariate analysis, the American Society of Anesthesiologists physical status, tumor differentiation, pathological Tumor, Node, Metastasis ... continue reading >>

Oncotarget: An exploratory biomarker study of COMPASS, a randomized phase II trial


Oncotarget Volume 11, Issue 30 reported that the authors hypothesized that if relevant biomarkers could be used to predict the suitable NAC regimen before treatment initiation, further improvements could be ensured in the outcomes of locally advanced GC.

mRNA extraction, real-time polymerase chain reaction, and immunohistochemical analyses were performed using endoscopic biopsy specimens of primary tumors, collected prior to NAC, to determine the clinically relevant biomarkers.

TIMP1, DSG2,... continue reading >>

Oncotarget: Down syndrome iPSC model: an endothelial perspective on tumor development


Oncotarget recently published "Down syndrome iPSC model: endothelial perspective on tumor development" which reported that the authors speculated that endothelial cells are active players in this clinical background.

To this end, they hypothesized that impaired DS endothelial development and functionality, impacted by genome-wide T21 alterations, potentially results in a suboptimal endothelial microenvironment with the capability to prevent solid tumor growth.

To test this hypothesis, an... continue reading >>

Oncotarget Journal Launches Special Collection on Breast Cancer


Oncotarget launched its first Special Collection of scientific publications directly related to breast cancer research in honor of breast cancer awareness.

BUFFALO, NY-November 18, 2020 – Each year, an estimated 40,000+ women and men lose the battle against breast cancer in the United States. After skin cancer, breast cancer is the most commonly diagnosed cancer in women.

Oncotarget launched the new Special Collections series on the free-to-read and rigorously peer-reviewed journal's website. ... continue reading >>

Oncotarget: MEK inhibitors relevant to SARS-CoV-2 infection


The cover for issue 46 of Oncotarget features Figure 6, "Establishment of a SARS-CoV-2 pseudovirus that expresses SPIKE protein variants on the envelope of a lentiviral core, infection of human airway epithelial cells or lung cancer cells, and demonstration of MEKi attenuation of infectivity on primary human cells," published in "MEK inhibitors reduce cellular expression of ACE2, pERK, pRb while stimulating NK-mediated cytotoxicity and attenuating inflammatory cytokines relevant to SARS-CoV-2... continue reading >>

Oncotarget: AKT isoforms have discrete expression in triple negative breast cancers


Oncotarget recently published "AKT isoforms have discrete expression in triple negative breast cancers and roles in cisplatin sensitivity" which reported that the authors investigated the expression and net effect of the individual isoforms in triple negative breast cancers and response to cisplatin treatment using cellular, mice models and clinical samples.

Interestingly, analysis of the expressions of AKT isoforms in clinical samples showed relatively higher expression of AKT1 in primary... continue reading >>

Oncotarget: IGF2 expression in breast cancer tumors and in breast cancer cells


The cover for issue 44 of Oncotarget features Figure 1, "Schematic diagram of the human IGF2 gene structure," by Radhakrishnan, et al. recently published in "Methylation of a newly identified region of the INS-IGF2 gene determines IGF2 expression in breast cancer tumors and in breast cancer cells" which reported that these authors previously demonstrated that IGF2 protein levels are higher in BC tissues from African American women than in Caucasian women.

They also showed that high IGF2... continue reading >>

Oncotarget: Targeting engineered cytokine with interleukin to the neovasculature of tumors


Oncotarget recently published "Targeting an engineered cytokine with interleukin-2 and interleukin-15 activity to the neovasculature of solid tumors" by Mortensen, et al. which reported that there is a growing interest in the antibody-based delivery of cytokines to the tumor environment as a means to boost the anti-cancer activity of tumor-resident T cells and NK cells.

Here, the authors described the expression and characterization of fusion proteins, featuring the L19 antibody and an... continue reading >>

Oncotarget: MEK is a promising target in the basal subtype of bladder cancer


Oncotarget recently published in "MEK is a promising target in the basal subtype of bladder cancer" by Merrill, et al. which reported that while many resources exist for the drug screening of bladder cancer cell lines in 2D culture, it is widely recognized that screening in 3D culture is more representative of in vivo response.

To address the need for 3D drug screening of bladder cancer cell lines, the authors screened 17 bladder cancer cell lines using a library of 652 investigational... continue reading >>

Oncotarget: Targeting breast cancer metabolism with a novel inhibitor


Oncotarget recently published "Targeting breast cancer metabolism with a novel inhibitor of mitochondrial ATP synthesis" by Kim, et al. which reported that the authors show that CADD522 inhibits mitochondrial oxidative phosphorylation by decreasing the mitochondrial oxygen consumption rate and ATP production in human breast cancer cells in a RUNX2-independent manner.

The enzyme activity of mitochondrial ATP synthase was inhibited by CADD522 treatment.

Differential scanning fluorimetry also... continue reading >>

Oncotarget: KDM5A and PHF2 positively control expression of pro-metastatic genes


The cover for Issue 43 of Oncotarget features Figure 6, "(A) Following the experimental protocol of Franzetti et al. [11] A673-shA1c cells −/+ Dox (EWS/Fli1high/EWS/Fli1low) were injected into the tail vein, and metastases were allowed to form in the absence of further Dox treatment (to allow recovery of cell growth in EWS/Fli1low cells)," recently published "KDM5A and PHF2 positively control expression of pro-metastatic genes repressed by EWS/Fli1, and promote growth and metastatic properties... continue reading >>

Oncotarget: Predictive biomarkers in Trop-2-expressing triple-negative breast cancer


Oncotarget recently published "Predictive biomarkers for sacituzumab govitecan efficacy in Trop-2-expressing triple-negative breast cancer" which reported that the authors investigated whether Trop-2-expression and homologous recombination repair of SN-38-mediated double-strand DNA breaks play a role in the sensitivity of triple-negative breast cancer to SG.

Further, two Trop-2-transfectants of MDA-MB-231, C13, and C39, were treated in mice with SG to determine whether increasing Trop-2... continue reading >>

Oncotarget: Heterogeneity of CEACAM5 in breast cancer


Oncotarget recently published "Heterogeneity of CEACAM5 in breast cancer" which reported that Here, we examined a repository of 110 cryopreserved primary breast carcinomas by immunohistochemistry to assess the distribution of CEACAM5 in tumor subtypes.

Assessing sample sets of paired primary breast cancers and corresponding lymph node lesions from a total of 59 patients revealed a high correlation between primary tumor and lymph node with regard to CEACAM5-status.

When examining the... continue reading >>

Oncotarget: Quantitative ultrasound radiomics in prediction of treatment response for breast cancer


The cover for Issue 42 of Oncotarget features Figure 4, "Generation of parametric and texture maps from radiofrequency data," recently published in "Quantitative ultrasound radiomics using texture derivatives in prediction of treatment response to neo-adjuvant chemotherapy for locally advanced breast cancer" by Dasgupta, et al. which reported that to investigate quantitative ultrasound based higher-order texture derivatives in predicting the response to neoadjuvant chemotherapy in patients with ... continue reading >>

Oncotarget: Hemoglobin increases the effectiveness of chemotherapy in lung cancer


Oncotarget recently published "Polymerized human hemoglobin increases the effectiveness of cisplatin-based chemotherapy in non-small cell lung cancer" which reported that unfortunately, a significant portion of NSCLC patients relapse due to cisplatin chemoresistance.

Administration of hemoglobin-based oxygen carriers is a promising strategy to alleviate hypoxia in the tumor, which may make cisplatin more effective.

The R-state PolyHb administered in this study is unable to deliver O2 unless... continue reading >>

Oncotarget: Combination of copanlisib with cetuximab improves tumor response


Oncotarget published "Combination of copanlisib with cetuximab improves tumor response in cetuximab-resistant patient-derived xenografts of head and neck cancer" which reported that HNSCC is frequently associated with either amplification or mutational changes in the PI3K pathway, making PI3K an attractive target, particularly in cetuximab-resistant tumors.

Here, the authors explored the antitumor activity of the selective, pan-class I PI3K inhibitor copanlisib with predominant activity... continue reading >>

Oncotarget: Evaluation of cancer-derived myocardial impairments using a mouse model


Oncotarget recently published "Evaluation of cancer-derived myocardial impairments using a mouse model" which reported that Myocardial damage in cancer patients is emphasized as a cause of death; however, there are not many murine cachexia models to evaluate cancer-derived heart disorder.

Using the mouse cachexia model that they established previously, the authors investigated myocardial damage in tumor-bearing mice.

When rat cardiomyoblasts were treated with mouse cachexia model ascites and... continue reading >>

Oncotarget: Melatonin increases overall survival of prostate cancer patients


Oncotarget recently published "Melatonin increases overall survival of prostate cancer patients with poor prognosis after combined hormone radiation treatment" which reported that a retrospective study included 955 patients of various stages of prostate cancer who received combined hormone radiation treatment from 2000 to 2019. Comprehensive statistical methods were used to analyze the overall survival rate of PCa patients treated with melatonin in various prognosis groups.

The overall... continue reading >>

Oncotarget: Exosomes secreted under hypoxia enhance stemness in Ewing's sarcoma


The cover for issue 40 of Oncotarget features Figure 5, "miR-210 silences the proapoptosis member CASP8AP2," by Kling, et al. which reported that hypoxic Ewing's sarcoma cells release exosomes that promote sphere formation, a stem-like phenotype, in EWS cells by enhancing survival.

Analysis of the hypoxic exosomal miRNA cargo identified a HIF-1α regulated miRNA, miR-210, as a potential mediator of sphere formation in cells exposed to hypoxic exosomes.

The knockdown of HIF-1α in hypoxic EWS... continue reading >>

Oncotarget: Simvastatin is a potential candidate drug in ovarian clear cell carcinomas


Oncotarget recently published "Simvastatin is a potential candidate drug in ovarian clear cell carcinomas" which reported that based on previous studies, the authors assessed the anti-proliferative effect of simvastatin, a Rho GTPase interfering drug, in three OCCC cell lines: JHOC-5, OVMANA and TOV-21G, and one high-grade serous ovarian cancer cell line, Caov3. The authors used the Rho GTPase interfering drug CID-1067700 as a control.

All OCCC cell lines were more sensitive to single-agent... continue reading >>

Oncotarget: Neuroendocrine carcinoma of uterine cervix findings shown by MRI


Oncotarget recently published "Neuroendocrine carcinoma of uterine cervix findings shown by MRI for staging and survival analysis – Japan multicenter study" which reported that to investigate neuroendocrine carcinoma of the uterine cervix cases for MRI features and staging, as well as pathological correlations and survival.

In 50 patients who underwent a radical hysterectomy and lymphadenectomy without neoadjuvant chemotherapy, intrapelvic T staging by MRI overall accuracy was 88.0% with... continue reading >>

Oncotarget: NRXN1 as a novel potential target for small cell lung cancer


The cover for issue 39 of Oncotarget features Figure 4, "Apoptosis assay of NRXN1-targeted ADC at IC50 dose calculated by growth inhibition curves," by Yotsumoto, et al. which reported that the authors identified transmembrane proteins overexpressed specifically in SCLC with little or no expression in normal tissues and decided to focus on the cell adhesion molecule neurexin-1.

The cell surface overexpression of NRXN1 was confirmed using flow cytometry in SCLC cell lines.

The combination of a ... continue reading >>

Oncotarget: Targeted lymphodepletion with a CD45-directed antibody radioconjugate


Oncotarget recently published "Targeted lymphodepletion with a CD45-directed antibody radioconjugate as a novel conditioning regimen prior to adoptive cell therapy" which reported that Chimeric antigen receptor T cell therapies, and adoptive cell therapy in general, represent one of the most promising anti-cancer strategies.

In contrast to relatively non-specific chemotherapy-derived lymphodepletion, targeted lymphodepletion with radioimmunotherapy directed to CD45 may be a safer and more... continue reading >>

Oncotarget: A comprehensive analysis of clinical trials in pancreatic cancer


The cover for issue 38 of Oncotarget features Figure 3, "Summary of the time and cost for drug development (modified from DiMasi et al [2016]," by Katayama, et al. which reported that Pancreatic cancer is the most aggressive common cancer and is desperately in need of novel therapies.

In this study, the Oncotarget authors perform the first comprehensive analysis of the current clinical trial landscape in pancreatic cancer to better understand the pipeline of new therapies.

In this study, ... continue reading >>

Oncotarget: Preventing colon 26 cancer-induced cardiorespiratory muscle weakness


Oncotarget recently published "Pharmacological targeting of mitochondrial function and reactive oxygen species production prevents colon 26 cancer-induced cardiorespiratory muscle weakness" which reported, that to determine if pharmacologically targeting mitochondrial dysfunction via treatment with the mitochondria-targeting peptide SS-31 would prevent cardiorespiratory muscle dysfunction, colon 26 adenocarcinoma tumor-bearing mice were administered either saline or SS-31 daily following... continue reading >>

Oncotarget: ATM inhibition overcomes resistance to histone deacetylase inhibitor


The cover for issue 37 of Oncotarget features Figure 7, "The combination of romidepsin and KU60019 is synergistic in a xenograft model of MCL," by Scotto, et al. which reported that the antiproliferative effect induced by histone deactylase inhibitors is associated with the up-regulated expression of the cyclin-dependent kinase inhibitor p21. Paradoxically, the increased expression of p21 correlates with a reduced cell killing to the drug.

HDAC inhibitors appear to activate p21 expression via... continue reading >>

Oncotarget: GATA3 and APOBEC3B are prognostic markers in adrenocortical carcinoma


The cover for issue 36 of Oncotarget features Figure 7, "Knockdown of APOBEC3B is associated with a lower tumor growth in an adrenocortical carcinoma xenograft mouse model," by Gara, et al. which reported that the role of APOBEC3B in adrenocortical carcinoma and the mechanisms through which its expression is regulated in cancer are not fully understood.

Here, the authors report that APOBEC3B is overexpressed in ACC and it regulates cell proliferation by inducing S phase arrest. They show high... continue reading >>

Secretomes from metastatic breast cancer cells, enriched for a prognostically unfavorable LCN2 axis, induce anti-inflammatory MSC actions and a tumor-supportive premetastatic lung


The cover for issue 32 of Oncotarget features Figure 5, "Model of potential mechanisms by which soluble factors from the primary breast tumors may induce an anti-inflammatory state within premetastatic tissues," by Meade, et al.

Mining transcriptome data from Py8119 and Py230 cells revealed a lipocalin 2 axis that is selectively expressed in the metastatic Py230 cells, predicts poor breast cancer patient survival and is elevated in circulating serum of mice chronically treated with conditioned ... continue reading >>

Oncotarget: The temporal effects of topical NF-κB inhibition: a preclinical model


The cover for issue 35 of Oncotarget features Figure 4, "The in vivo pre- or post- topical application of BAY 11-7082 prevents the acidic bile-induced deregulation of cancer-related miRNA markers in 10-day exposed murine HM," by Vageli, et al. reported that Supraesophageal bile reflux at strongly acidic pH can cause hypopharyngeal squamous cell cancer, through activation of the oncogenic NF-κB-related pathway.

The authors hypothesize that topical pre- or post-application of pharmacologic NF-κB ... continue reading >>

Oncotarget: Ghrelin ameliorates tumor-induced adipose tissue atrophy and inflammation


Oncotarget Volume 11, Issue 35 published "Ghrelin ameliorates tumor-induced adipose tissue atrophy and inflammation via Ghrelin receptor-dependent and -independent pathways" by Liu et. al which reported that Ghrelin has been proposed as a treatment for cancer cachexia partly by preventing AT atrophy.

This study characterizes the pathways involved in AT atrophy in the Lewis Lung Carcinoma -induced cachexia model and those mediating the effects of ghrelin in Ghsr / and Ghsr–/– mice.

Ghrelin... continue reading >>

Oncotarget: Triggering apoptotic cell death in skin cancer


Oncotarget Volume 11, Issue 35 published "Targeting 14-3-3ε-CDC25A interactions to trigger apoptotic cell death in skin cancer" by Holmes et, al. which reported that the authors previously documented an anti-apoptotic role for CDC25A in cutaneous squamous cell carcinoma, an activity dependent on its association with 14-3-3 proteins.

The authors hypothesized that targeting CDC25A-14-3-3ε interactions may be an effective strategy for inducing skin cancer cell apoptosis.

Co-immunoprecipitation... continue reading >>

Oncotarget: Therapeutic applications of SH7139 extend beyond non-Hodgkin's lymphoma


Oncotarget Volume 11, Issue 35 published "Therapeutic applications of the selective high affinity ligand drug SH7139 extend beyond non-Hodgkin's lymphoma to many other types of solid cancers" by Balhorn et, al. which reported that SH7139, the first of a series of selective high affinity ligand oncology drug candidates designed to target and bind to the HLA-DR proteins overexpressed by B-cell lymphomas, has demonstrated exceptional efficacy in the treatment of Burkitt lymphoma xenografts in mice ... continue reading >>

Oncotarget: Sequencing interdisciplinary molecular tumor board in breast cancer patients


Oncotarget Volume 11, Issue 35 published "Sequencing for an interdisciplinary molecular tumor board in patients with advanced breast cancer–experiences from a case series" by Walter et, al. which reported that although prognosis of patients with early breast cancer has improved over the last decades, metastatic breast cancer remains incurable.

Despite increasing therapeutic options regarding systemic treatment, predicting efficacy of a targeted drug on a patient level is still challenging.... continue reading >>

Oncotarget: Paradox breaker BRAF inhibitors in BRAF mutant colorectal cancer


Oncotarget Volume 11, Issue 34 features Figure 1, "BRAF inhibitor-induced changes in cell viability," by Pickles, et which reported that the BEACON CRC trial demonstrated a survival advantage over chemotherapy for a combination of targeted agents comprising the potent BRAF inhibitor encorafenib together with cetuximab and binimetinib.

Resistance to BRAF inhibition in CRC arises in part through the generation and activation of RAF dimers resulting in MEK-ERK pathway reactivation.

The... continue reading >>

Oncotarget: An integrative microenvironment approach for follicular lymphoma


Oncotarget Volume 11, Issue 33 features Figure 8, "Haplotype estimates in follicular lymphoma patients," by Assis-Mendonça, et al. which reported that the authors tested associations between SNPs, clinicopathological features and TME composition, and proposed survival models in R-CHOP/R-CVP-treated patients.

Presence of the IL12A rs568408 “A” allele associated with the follicular pattern of FOXP3 cells.

The IL12A AA haplotype included rs583911 and rs568408 and was an independent predictor of... continue reading >>

Oncotarget: Survival after resection of brain metastases: A matched cohort analysis


The cover for issue 32 of Oncotarget features Figure 2, "This figure depicts overall survival and local in-brain recurrence-free survival in the study's subgroups," by Hussein, et al. which reported that the aim of the present study is to assess whether the use of 5-ALA has an impact on local recurrence or survival compared to conventional white light microscopic tumor resection.

Two groups were compared:

     In the “white light” group, resection was performed with conventional microscopy.

 ... continue reading >>

Oncotarget: Induction of phenotypic changes in HER2-postive breast cancer cells


The cover for issue 30 of Oncotarget features Figure 4, "RNAseq results demonstrating differences between normal, cancer, and redirected cells," by Frank-Kamenetskii, et al. which reported that the influence of breast cancer cells on normal cells of the microenvironment, such as fibroblasts and macrophages, has been heavily studied but the influence of normal epithelial cells on breast cancer cells has not.

Here using in vivo and in vitro models the Oncotarget authors demonstrate the impact... continue reading >>

Oncotarget: cGAS-STING pathway in oncogenesis and cancer therapeutics


Oncotarget Volume 11, Issue 30 reported that recent evidence shows that the host innate immunity is also critical in sensing the presence of cytoplasmic DNA derived from genomic instability events, such as DNA damage and defective cell cycle progression.

This is achieved through the cyclic GMP-AMP synthase /Stimulator of interferon genes pathway.

Here the Oncotarget authors discuss recent insights into the regulation of this pathway in cancer immunosurveillance, and the downstream signaling... continue reading >>

Oncotarget: Inhibition of HAS2 and hyaluronic acid production by 1,25-Dihydroxyvitamin D3 in breast cancer


Oncotarget Volume 11, Issue 30 reported that genomic profiling of murine mammary tumor cells with differential VDR expression identified 35 transcripts that were altered by the 1,25D3-VDR complex including Hyaluronan Synthase-2.

Here the Oncotarget authors confirmed that 1,25D3 reduces both HAS2 gene expression and hyaluronic acid synthesis in multiple models of breast cancer.

HAS2 expression and HA production are elevated in immortalized human mammary epithelial cells induced to undergo... continue reading >>

Oncotarget: Th1 cytokines potentiate apoptosis of breast cancer cells and suppress tumor growth


Volume 11, Issue 30 of Oncotarget reported that previously, the authors showed that anti-estrogen drugs combined with a dendritic cell-based anti-HER-2 vaccine known to induce strong Th1-polarized immunity dramatically improved clinical response rates in patients with HER-2pos/ERpos early breast cancer.

Here, the Oncotarget authors show that the small molecule Akt antagonist MK-2206, when combined with the Th1 cytokines IFN-gamma and TNF-alpha, maximize indicators of apoptotic cell death in a... continue reading >>

Oncotarget: Exosomal lncRNA PCAT-1 promotes Kras-associated chemoresistance


Oncotarget Volume 11, Issue 29 reported that Immunosuppressive chemoresistance is a major burden in lung cancer.

Recent data reveal that long noncoding RNAs present in the lung tumor microenvironment are implicated in chemoresistant-related immune deregulation, and metastasis but their exact pathogenic role is still unknown.

In this study, the Oncotarget authors investigate the role of lncRNA PCAT-1 in chemoresistant immunosuppression and its involvement in tumor stroma remodeling. Findings... continue reading >>

Oncotarget: Genomic markers of midostaurin drug sensitivity in leukemia patients


Oncotarget Volume 11, Issue 29 reported that acute myeloid leukemia is a heterogeneous malignancy with the most common genomic alterations in NPM1, DNMT3A, and FLT3. Midostaurin was the first FLT3 inhibitor FDA approved for AML and is standard of care for FLT3 mutant patients undergoing induction chemotherapy.

As there is a spectrum of response, we hypothesized that biological factors beyond FLT3 could play a role in drug sensitivity and that select FLT3-ITD negative samples may also... continue reading >>

Oncotarget: Therapeutic efficacy of liposomal Grb2 antisense oligodeoxynucleotide (L-Grb2)


The cover for issue 29 of Oncotarget features Figure 5, "In vivo effects of treatment with L-Grb2 in combination with anti-angiogenic therapy in an ovarian tumor model," by Lara, et al. which reported that adaptor proteins such as growth factor receptor-bound protein-2 play important roles in cancer cell signaling. In the present study, the authors examined the biological effects of liposomal antisense oligodeoxynucleotide that blocks Grb2 expression in gynecologic cancer models.

Murine... continue reading >>

Oncotarget: Geriatric nutritional risk index - prognostic marker of esophageal carcinoma


Oncotarget Volume 11, Issue 29 reported that In multivariate analyses, serum albumin, GNRI, pathological tumor-node-metastasis stage, and tumor differentiation were independent prognostic factors for CSS.

In pTNM stage I, multivariate analysis identified C-reactive protein and GNRI as independent prognostic factors for CSS.

In univariate analyses in pTNM stages II and III, only low GNRI and low serum albumin levels, respectively, were significantly associated with worse CSS.

In patients with ... continue reading >>

Oncotarget: The Golgi protein TMEM165 controls migration/invasion for carcinoma


The cover for issue 28 of Oncotarget features Figure 5, "TMEM165 expression levels alters N-linked glycosylation," by Murali, et al., and reported that the TMEM165 protein was not detected in non-malignant matched breast tissues and was detected in invasive ductal breast carcinoma tissues by mass spectrometry.

The hypothesis is that the TMEM165 protein confers a growth advantage to breast cancer.

The authors created a CRISPR/Cas9 knockout of TMEM165 in the human invasive breast cancer cell... continue reading >>

Oncotarget: Rapid onset type 1 diabetes with anti-PD-1 directed therapy


Volume 11, Issue 28 of Oncotarget features "Rapid onset type 1 diabetes with anti-PD-1 directed therapy", by Yun et al. and reported that Type 1 diabetes is a rare immune-related adverse event caused by checkpoint inhibitors with serious risk for diabetic ketoacidosis.

Of the patients who received immunotherapy, 5 patients were found to have type 1 diabetes, all of whom presented with DKA requiring insulin at 20 to 972 days from their first anti-PD- 1 dose.

Four patients had new-onset... continue reading >>

Oncotarget: Characterization of porcine hepatocellular carcinoma for liver cancer


Volume 11, Issue 28 of Oncotarget features "Development and comprehensive characterization of porcine hepatocellular carcinoma for translational liver cancer investigation" by Gaba et, al. which reported that reliable development of Oncopig HCC cell lines was demonstrated through hepatocyte isolation and Cre recombinase exposure across 15 Oncopigs.

Oncopig and human HCC cell lines displayed similar cell cycle lengths, alpha-fetoprotein production, arginase-1 staining, chemosusceptibility, and... continue reading >>

Oncotarget: Cooperative tumorigenic effects of targeted deletions of tumor suppressors


Volume 11, Issue 28 of Oncotarget features "Genetic analysis of the cooperative tumorigenic effects of targeted deletions of tumor suppressors Rb1, Trp53, Men1, and Pten in neuroendocrine tumors in mice" by Xu et, al. which reported that the authors examined whether the TSGs Rb1, Trp53, Pten, and Men1 have cooperative effects in suppressing neuroendocrine tumors in mice.

By monitoring growth and examining the histopathology of the pituitary and pancreas in these mice, the authors demonstrated... continue reading >>

Oncotarget: Tumor markers for carcinoma identified by imaging mass spectrometry


Volume 11, Issue 28 of Oncotarget features "Lipid and protein tumor markers for head and neck squamous cell carcinoma identified by imaging mass spectrometry" by Schmidt et, al. which reported that the authors used MALDI imaging mass spectrometry and immunohistochemistry to seek tumor-specific expression of proteins and lipids in HNSCC samples.

Among low molecular weight proteins visualized, S100A8 and S100A9 were found to be expressed in the regions of tumor tissue but not in the surrounding... continue reading >>

A 3D biofabricated cutaneous squamous cell carcinoma tissue model


The cover for issue 27 of Oncotarget features Figure 4, "(A) Bimodal imaging examples of control and treated tumors (red) before and after the treatment period," by Browning, et al. and reported that the authors developed a 3-dimensional bioprinted skin model of cutaneous squamous cell carcinoma (cSCC) tumors together with a microscopy assay to test chemotherapeutic effects in tissue.

Fluorescence-derived imaging biomarkers indicated that 50% of cancer cells were killed in the tissue after 1μM ... continue reading >>

Oncotarget: Epigenetic feedback and stochastic partitioning can drive resistance to EMT


Oncotarget Volume 11, Issue 27 published "Epigenetic feedback and stochastic partitioning during cell division can drive resistance to EMT" by Jia et al. which reported that Epithelial-mesenchymal transition (EMT) and its reverse process mesenchymal-epithelial transition are central to metastatic aggressiveness and therapy resistance in solid tumors.

While molecular determinants of both processes have been extensively characterized, the heterogeneity in the response of tumor cells to EMT and... continue reading >>

Oncotarget: Australian experience of peptide receptor radionuclide therapy


Oncotarget Volume 11, Issue 27 published "Australian experience of peptide receptor radionuclide therapy in lung neuroendocrine tumours" by Lim et al. which reported peptide receptor radionuclide therapy (PRRT) is an approved treatment modality for gastroenteropancreatic neuroendocrine tumours, although Phase III randomised clinical trial data is not available for NETs of other site of origin, in practice, PRRT is used more widely in clinical practice, based on its mechanism of targeting the... continue reading >>

Oncotarget: Clonality and antigen-specific responses shape prognostic effects


Oncotarget Volume 11, Issue 27 published "Clonality and antigen-specific responses shape the prognostic effects of tumor-infiltrating T cells in ovarian cancer" by Tsuji et al. which reported that to delineate the complexity of anti-tumor T-cell responses, the author's utilized a computational method for de novo assembly of sequences from CDR3 regions of 369 high-grade serous ovarian cancers from TCGA, and then applied deep TCR-sequencing for analyses of paired tumor and peripheral blood... continue reading >>

Oncotarget: Correction of NSE concentration improves diagnostic accuracy in lung cancer


Oncotarget Volume 11, Issue 27 published "Correction of the NSE concentration in hemolyzed serum samples improves its diagnostic accuracy in small-cell lung cancer" by Genet et al. which reported that this study aimed to develop a hemolysis correction equation and evaluate its role in small-cell lung cancer (SCLC) diagnostics.

A hemolysis correction equation was obtained by analyzing the relationship between the measured Neuron-specific enolase (NSE) concentration and the degree of hemolysis.

... continue reading >>

Oncotarget: Development & characterization of COS-33 with activation of mTOR pathway


Oncotarget recently published "Development and characterization of the novel human osteosarcoma cell line COS-33 with sustained activation of the mTOR pathway" which reported that the successful establishment of a new human osteosarcoma cell line, COS-33, from a patient-derived xenograft and demonstrate retention of the biological features of the original tumor.

The Oncotarget authors found high mTOR signaling activity in the cultured cells, which were sensitive to a small molecule inhibitor,... continue reading >>

Oncotarget: miR-708-5p targets oncogenic prostaglandin E2 production in lung cancer cell


Volume 11, Issue 26 of Oncotarget reported that Lung cancer is of particular importance, as it is the deadliest cancer worldwide.

In this study, the authors show that high mi R-708 expression is associated with survival rates in lung squamous cell carcinoma patients. mi R-708 also represses PGE2 production by suppressing both COX-2 and mPGES-1 expression in lung cancer cells.

Moreover, mi R-708 decreases proliferation, survival, and migration of lung cancer cells, which can be partially... continue reading >>

Oncotarget: The role of miRNA-133b and its target gene SIRT1 in FAP-derived desmoid tumor


Volume 11, Issue 26 of Oncotarget reported that in this study the authors studied the differences in mi RNA expression between sporadic and FAP-associated Desmoid tumors using microarray confirmed by quantitative PCR.

Among them, mi R-133b levels were significantly lower in FAP-associated Desmoid tumors than in sporadic Desmoid tumors. The qPCR analysis showed that SIRT1 mRNA levels were significantly up-regulated in FAP-associated Desmoid tumor than in sporadic Desmoid tumor, whereas no... continue reading >>

Oncotarget: IQGAP1 control of centrosome function defines variants of breast cancer


The cover for issue 26 of Oncotarget features Figure 6, "Mislocalization of IQGAP1-BRCA1 in human TNBC tumors phenocopies the dominant mutants and the TNBC cells," by Osman, et al. and reported that IQGAP1 is a signaling scaffold implicated in TNBC, but its mechanism is unknown.

Genetic mutant analyses suggest that phosphorylation cycling of IQGAP1 is important to its subcellular localization and centrosome-nuclear shuttling of BRCA1; dysfunction of this process defines two alternate... continue reading >>

Oncotarget: Bacteriome and mycobiome and bacteriome-mycobiome interactions


Volume 11 Issue 25 of @Oncotarget reported that the authors aimed to characterize the bacteriome, mycobiome, and mycobiome-bacteriome interactions of oral wash in Head and neck squamous cell carcinoma, or HNSCC, patients and to determine if they are distinct from those of the oral wash of matched non-Head and neck squamous cell carcinoma patients.

Oral wash samples were collected from 46 individuals with HNSCC and 46 controls for microbiome analyses.

A number of organisms were identified as... continue reading >>

Oncotarget: Tumor suppressor p53 regulates insulin receptor gene expression


Volume 11, Issue 25 of @Oncotarget reported that the present study was aimed at evaluating the hypothesis that p53 governs the expression and activation of the INSR gene in breast cancer cells.

The availability of MCF7 breast cancer-derived cell lines with specific disruption of either the insulin-like growth factor-1 receptor or INSR allowed us to address the impact of the IGF1R and INSR pathways on p53 expression.

Wild-type p53 stimulated INSR promoter activity in control cells while... continue reading >>

Oncotarget: Mutation profile of primary subungual melanomas in Caucasians


Volume 11 Issue 25 of @Oncotarget reported that this study aimed to define the mutation profile of SUM in Caucasians.

Next-generation sequencing-based genomic analysis was used to identify frequently mutated loci in 50 cancer-related genes in 31 SUM primary tumors.

The most abundant mutations in SUM were found in KIT – in 13% of cases and NRAS – also in 13%, while BRAF - only in 3% of cases.

The authors' findings confirmed a high frequency of KIT and NRAS mutations in SUM, as well as a low... continue reading >>

Oncotarget: Indoximod opposes the immunosuppressive effects mediated by IDO and TDO


Volume 11 Issue 25 of @Oncotarget reported that Indoximod has shaped the understanding of the biology of IDO1 in the control of immune responses, though its mechanism of action has been poorly understood.

Indoximod can have a direct effect on T cells, increasing their proliferation as a result of mTOR reactivation.

Further, indoximod modulates the differentiation of CD4+ T cells via the aryl hydrocarbon receptor, which controls transcription of several genes in response to different ligands... continue reading >>

Postoperative atrial fibrillation does not impact on overall survival after esophagectomy


Volume 11, Issue 25 of @Oncotarget reported that Administration of landiolol hydrochloride was found to be associated with reduced incidence of atrial fibrillation after esophagectomy for esophageal cancer in our previous randomized controlled trial.

Between March 2014 and January 2016, 100 patients with esophageal cancer were registered in an RCT trial and randomly allocated to receive either administration of landiolol or a placebo.

The authors analyzed data from this RCT to better... continue reading >>

Oncotarget: RSK inhibitor BI-D1870 inhibits acute myeloid leukemia cell proliferation


Volume 11, Issue 25 of @Oncotarget reported that to examine the role of RSK in AML, the authors analyzed apoptosis and the cell cycle profile following treatment with BI-D1870, a potent inhibitor of RSK. BI-D1870 treatment increased the G2/M population and induced apoptosis in Acute Myeloid Leukemia cell lines and patient Acute Myeloid Leukemia cells.

Therefore, the authors investigated whether BI-D1870 potentiates the anti-leukemic activity of vincristine by targeting mitotic exit.

Combinatio... continue reading >>

Oncotarget: Preoperative geriatric nutritional risk index is a useful prognostic indicator


The cover for issue 24 of Oncotarget features Figure 4, "Cancer-specific survival curves based on GNRI according to pTNM stage," by Hirahara, et al.

Volume 11 Issue 24 of @Oncotarget reported that this study aimed to evaluate the relationship between preoperative Geriatric Nutritional Risk Index and long-term outcomes in elderly gastric cancer patients.

  • In the univariate analyses, OS was significantly associated with the American Society of Anesthesiologists Physical Status,
... continue reading >>

Oncotarget: Active targeting for photodynamic therapy treatment of breast cancer cells


Volume 11, Issue 22 of @Oncotarget reported that targeted Photodynamic therapy is a non-invasive and site-specific treatment modality, which has been utilized to eradicate cancer tumor cells with photoactivated chemicals or photosensitizers, in the presence of laser light irradiation and molecular tissue oxygen.

Breast cancer is the most common cancer among women worldwide and is currently treated using conventional methods such as chemotherapy, radiotherapy, and surgery.

Despite the recent... continue reading >>

Oncotarget: Exploring the role of survivin in neuroendocrine neoplasms


Volume 11, Issue 23 of @Oncotarget reported that tissue microarrays of 132 patients were stained for survivin using immunohistochemistry and correlated with outcomes.

Using a genomic database, the authors then correlated survivin mRNA expression with the radiosensitivity index in 52 samples of Neuroendocrine tumors. Finally, they studied the effect of radiation on survivin expression in human cell lines and the impact of knock-down of BIRC5 on cell proliferation and radiation sensitivity.

The ... continue reading >>

Oncotarget: Hereditary pancreatitis model by blastocyst complementation in mouse


Volume 11, Issue 22 of @Oncotarget reported that the application of pluripotent stem cells is expected to contribute to the elucidation of the unknown mechanism of human diseases.

To study the mechanism of human hereditary pancreatitis, the authors here performed the blastocyst complementation method.

In the BC method, mouse embryonic stem cells harboring CRISPR/CAS9-mediated mutations in the Prss1 gene were injected into blastocysts with a deficient Pdx1 gene, which is a critical... continue reading >>

Oncotarget: Efficacy of osimertinib against EGFRvIII+ glioblastoma


Volume 11, Issue 22 of @Oncotarget reported that the present study examined the effects of osimertinib on EGFRv III+ Glioblastoma models, both in vitro and in vivo.

Therefore, a panel of six Glioblastoma stem cells expressing EGFRv III+ was evaluated.

The EGFRv III+ GSC differed in the expression of EGFRv III and other key genes.

The GSC line D317, which expresses high levels of EGFRv III and has robust tyrosine kinase activity, was selected for assessing osimertinibs efficacy.

Herein, the... continue reading >>

Oncotarget: miR-151a enhances Slug dependent angiogenesis


Volume 11, Issue 23 of @Oncotarget reported that the authors have previously established that mi R-151a functions as an onco-mi R in non-small cell lung cancer cells by inducing partial EMT and enhancing tumor growth.

Here, the authors identify anti-mi R-151a as a molecule that promotes endothelial cell contacts and barrier properties, suggesting that mi R-151a regulates cell-cell junctions.

They find that induced mi R-151a expression enhances endothelial cell motility and angiogenesis and... continue reading >>

Oncotarget: Stemness genes and the capacity of breast tumors for metastasis


Volume 11, Issue 21 of @Oncotarget reported that using primary cultures from the breast tumor of patient St23784/17 with stemness gene amplification and patient Ti41749/17 without stemness gene amplification in the tumor, the research team studied the expression of stemness genes, proliferative tumor stem-cell activity, mammosphere formation, and expression of the CD44 tumor stem cell marker.

Primary cultures of Ep Cam+ tumor cells from patients with stemness gene amplifications revealed high... continue reading >>

Oncotarget: The role of EGFR mutations in predicting recurrence in lung adenocarcinoma


Volume 11, Issue 22 of @Oncotarget reported that while lobectomy can improve mortality in this group, about 30 55% of patients will experience disease recurrence.

The increased investigation into the factors affecting recurrence, particularly tumor molecular genetics such as EGFR mutations, is needed.

These authors conducted a single-center retrospective study of 282 patients with early or locally advanced lung adenocarcinoma, with or without EGFR mutations, who underwent definitive therapy.

... continue reading >>

Oncotarget: BCATc regulating proliferation in triple-negative breast cancer


Volume 11, Issue 21 of @Oncotarget reported that as nutrient levels of BCAAs, substrates of BCATc, regulate the PI3K/Akt pathway and the authors hypothesized that increased expression of BCATc would contribute to tumor cell growth through upregulation of the insulin/IGF-1 signaling pathway.

An analysis of this pathway showed that when overexpressed BCATc regulates proliferation through the PI3K/Akt axis, whilst simultaneously attenuating the Ras/Erk pathway indicating that BCATc acts as a... continue reading >>

Oncotarget: Adoptive cell therapy in combination with checkpoint inhibitors


Volume 11, Issue 22 of @Oncotarget reported that there are rationale and evidence supporting immune therapy in Ovarian Cancers. The authors investigated the potential for adoptive cell therapy from in vitro expanded tumor-infiltrating lymphocytes in combination with checkpoint inhibitors and conducted immunological testing of ex vivo expanded TILs.

Six patients with late-stage metastatic high-grade serous Ovarian Cancer were treated with immune therapy consisting of ipilimumab followed by... continue reading >>

Oncotarget: TAK1 regulates the tumor microenvironment


Volume 11, Issue 21 of @Oncotarget reported that in this study the authors evaluated the potential therapeutic capacity of TAK1 inhibition on tumor growth and on tumor microenvironment remodeling.

In a screen of 16 cancer cell lines, takinib in combination with tumor necrosis factor was found to induce cell death in 6 out of 16 cell lines.

Histological and proteomic analysis of TAK1KO tumors showed altered angiogenic signaling and inflammatory signaling via immune cells.

Dr. Timothy A.J.... continue reading >>

Oncotarget: Hyperprogression to immune blockade followed by a response with cabozantinib


Volume 11, Issue 22 of @Oncotarget reported that more and more patients receive first-line treatment with immunotherapy combinations and not all patients respond in metastatic renal cell carcinoma.

After IO-IO progression, the authors stated “we do not have a standard of treatment because it is not available for prospective data on this setting.

Therefore the authors present the case of a patient with metastatic renal cell carcinoma who suffered hyperprogression with IO-IO combination in the ... continue reading >>

Oncotarget: Influence of the progression of pleural neoplasia on outcome of pleurodesis


Volume 11, Issue 22 of Oncotarget reported that the goal of this study was to explore the involvement of mi RNAs in beneficial effects exerted by physical activity in breast cancer prevention.

The levels of extracellular mi RNAs were evaluated in blood plasma before and after structured exercise by means of microarray analysis of 1,900 mi RNAs identifying mostly modulated mi RNAs. The different expressions of two mi RNAs involved in breast cancer progression, i. e. up-regulation of mi R-206... continue reading >>

Oncotarget: Second line trastuzumab emtansine following horizontal dual blockade


Volume 11, Issue 22 of Oncotarget reported that despite relevant medical advancements, metastatic breast cancer remains an incurable disease.

HER2 signaling conditions tumor behavior and treatment strategies of HER2 expressing breast cancer.

Cancer treatment guidelines uniformly identify dual blockade with pertuzumab and trastuzumab plus a taxane as best first line and trastuzumab emtansine as a preferred second-line choice.

However, there is no prospectively designed available study... continue reading >>

Oncotarget: Anticancer effect of physical activity is mediated


Volume 11, Issue 22 of Oncotarget reported that the goal of this study was to explore the involvement of mi RNAs in beneficial effects exerted by physical activity in breast cancer prevention.

The levels of extracellular mi RNAs were evaluated in blood plasma before and after structured exercise by means of microarray analysis of 1,900 mi RNAs identifying mostly modulated mi RNAs. The different expressions of two mi RNAs involved in breast cancer progression, i. e. up-regulation of mi R-206... continue reading >>

Oncotarget: An exploratory study of metformin and rapamycin as maintenance therapy


Volume 11, Number 21 of @Oncotarget reported that eligible patients with stable or responding mPDA after 6 months on chemotherapy were randomized 1:1 to metformin alone or with rapamycin, stratified by prior treatment with FOLFIRINOX. Metformin +/ rapamycin maintenance for mPDA was well-tolerated and several patients achieved stable disease associated with exceptionally long survival.

Dr. Dung T. Le from The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, 21287 said, ... continue reading >>

Oncotarget: Muscle mass, not radiodensity, predicts physical function in cancer patients


Volume 11, Issue 20 of @Oncotarget reported that this study aimed to establish the relationship between computed tomography -derived muscle cross-sectional area, radiodensity, and skeletal muscle index and dual-energy X-ray absorptiometry parameters with functional performance in cancer patients.

In cancer patients, DXA ALM and CT muscle CSA each predicted physical function; muscle radiodensity did not, and DXA ALM explained more variability in SCP and 1RM than CT muscle CSA.

Dr. Jose M.... continue reading >>

Immunotherapy of ovarian cancer with a monoclonal antibody


Epithelial ovarian carcinoma (EOC) is the most prevalent and lethal form of ovarian cancer. An array of non-definitive symptoms associated with the onset of EOC and the lack of effective biomarkers for early detection often results in late diagnoses at advanced diseased stages resulting in high rates of disease recurrence and poor prognoses even after treatment with current standard of care that typically includes platinum-based drugs. Although often effective initially, toxicity and/or... continue reading >>

Oncotarget: Entinostat augments NK cell functions via epigenetic upregulation


Volume 11, Issue 20 of @Oncotarget reported that the authors evaluated the impact of a benzamide HDACi, entinostat, on human primary NK cells as well as tumor cell lines.

Additionally, entinostat increased both cytotoxicity and IFN- production in human NK cells following coculture with these tumor cells.

Dr. Monica S. Thakar from The Laboratory of Molecular Immunology and Immunotherapy, Blood Research Institute, Versiti and The Division of Pediatric Hematology-Oncology-BMT, Department of... continue reading >>

Oncotarget: Pineal gland protects against oral carcinogenesis and tumor progression


Volume 11, Issue 20 of @Oncotarget reported that no study evaluated the influence of pinealectomy on oral cancer development.

Then, in the current study, they investigated the effects of pinealectomy on oral squamous cell carcinoma occurrence and progression in rats.

The melatonin suppression caused by the pinealectomy might contribute to oral cancer development by acting on ERK1/2 and p53 pathways and regulating tumor inflammation.

Dr. Daniel Galera Bernabé from The Psychoneuroimmunology... continue reading >>

Oncotarget: Metastatic clear cell renal carcinoma treated with surgery and Cabozantinib


Volume 11, Issue 20 of @Oncotarget reported that the aim of this article is to describe the case of metastatic recurrent RCC with sarcomatoid dedifferentiation in a 59-year-old male patient treated with nephrectomy and multiple metastasectomies followed by Cabozantinib.

Surgery for metastases followed by Cabozantinib may be a therapeutic option in metastatic young patients.

Dr. Johnny Boustany from The Notre Dame des Secours University Hospital Center (CHUNDS) as well as The Holy Spirit... continue reading >>

Exosome-mediated delivery of mi R-30a sensitize cisplatin-resistant variant of oral squamous carcinoma cells via modulating Beclin1 and Bcl2


Volume 11, Issue 20 of @Oncotarget reported that in conjunction with the findings in clinical samples, decreased mi R-30a expression was observed in vitro in the cisplatin-resistant cultured OSCC cells compared to the cisplatin-sensitive cells.

Besides, the authors identified Beclin1, an autophagy-related marker, as a target of mi R-30a and found it to be overexpressed in cisplatin-resistant OSCC cells, thus indicating at its possible negative-regulation by mi R30a.

Exosomes from the... continue reading >>

Oncotarget: Knock-down of the TIM/TIPIN complex promotes apoptosis in melanoma cells


Volume 11, Issue 20 of @Oncotarget reported that recent studies revealed the involvement of TIM and TIPIN in human malignancies; however, no evidence is available regarding the expression of the TIM/TIPIN protein complex or its potential role in melanoma.

To assess the role of the TIM/TIPIN complex in melanoma, The Dong research team analyzed TIM/TIPIN expression data from the publicly accessible TCGA online database, Western blot analysis, and RT-qPCR in a panel of melanoma cell lines.

The... continue reading >>

Oncotarget: PLAC1 essential for FGF7/FGFRIIIb-induced Akt-mediated cell proliferation


Volume 11, Issue 20 of @Oncotarget reported that the Research Team studied human choriocarcinoma and breast cancer cell lines to explore the localization and receptor-ligand interactions, as well as the downstream effects of PLAC1.

They further show that PLAC1 signaling via FGFR2IIIb activates AKT phosphorylation in cancer cell lines.

Dr. Ugur Sahin from TRON–Translational Oncology at the University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany said, "Placental... continue reading >>

Oncotarget: Aberrant epigenetic silencing of neuronatin - a frequent event in osteosarcoma


The cover for issue 20 of @Oncotarget features Figure 5, "Neuronatin protein expression is detectable in normal bone and cartilage tissues," by Saeed, et al.

It reported that the expression of NNAT was detectable in osteoblasts and chondrocytes of human bone, supporting a potential role in bone homeostasis.

Enforced expression of NNAT in human OS cells lacking endogenous expression resulted in a significant reduction in colony formation and in vitro migration compared to nonexpressor control... continue reading >>

Combination of ATO with FLT3 TKIs eliminates FLT3/ITD+ leukemia cells through reduced expression of FLT3


The cover for issue 68 of Oncotarget features Figure 6G, "Summary of the mechanisms for the synergistic combination of ATO and FLT3 TKIs in FLT3 mutant AML cells," by Nagai, et al.

The research team explored the feasibility of combining FLT3 TKIs with ATO in the treatment of FLT3/ITD+ leukemias. Furthermore, ATO combined with sorafenib, a FLT3 TKI, in vivo reduced growth of FLT3/ITD+ leukemia cells in NSG recipients. In conclusion, these results suggest that ATO is a potential candidate to... continue reading >>

Knock-in of the Wt1 R394W mutation causes MDS and cooperates with Flt3/ITD to drive aggressive myeloid neoplasms in mice


The cover for issue 82 of Oncotarget features Figure 5B, "Kaplan–Meier survival curve of the transplanted mice," by Annesley, et al.

Here, the research team described the hematologic phenotype of a knock-in mouse model of a Wt1 mutation, described in cases of human leukemia. They crossbred Wt1+/R394W mice with knock-in Flt3+/ITD mice, and show that mice with both mutations develop a transplantable MDS/MPN, with more aggressive features compared to either single mutant mouse model.

Dr. Patrick ... continue reading >>

NFk B drives stemness and resistance to therapy in ER+HER2- breast cancer


Volume 11, Number 19 of @Oncotarget reported that RANK pathway affects the expression of cell cycle regulators and decreases sensitivity to fulvestrant of estrogen receptor-positive /HER2- breast cancer cells, MCF-7 and T47D.

These results suggest that ER+HER2- RANK-positive cells may constitute an important reservoir of slow cycling, therapy-resistance cancer cells; and that RANK pathway activation is deleterious in all ER+HER2- breast cancer cells, independently of RANK levels.

Dr. Sandra... continue reading >>

Radiation induces iatrogenic immunosuppression by indirectly affecting hematopoiesis


Volume 11, Number 19 of @Oncotarget reported that the research team found that irradiated cells traffic to the bone marrow and bring about the reduction of hematopoietic stem cells and progenitor cells.

RNA Sequencing and gene set enrichment analysis of the bone marrow cells following irradiation showed down-regulation of genes involved in hematopoiesis.

Dr. Dinesh Thotala from The Department of Radiation Oncology as well as The Siteman Cancer Center, St. Louis School of Medicine both at The... continue reading >>

Synergistic effects of BET and MEK inhibitors promote regression of anaplastic thyroid tumors


The cover for issue 83 of Oncotarget features Figure 4, "Trametinib and the combined treatment of JQ1 and trametinib inhibit ATC cell migration," by Zhu, et al.

Combined treatment suppressed MYC expression more than single treatment, resulting in decreased expression of pro-survival regulators and increased pro-apoptotic regulators to collaboratively induce apoptosis.

In xenograft studies, single treatment only partially inhibited tumor growth, but the combined treatment inhibited tumor... continue reading >>

Oncotarget Association of germline genetic variants with TMPRSS2-ERG fusion status


Oncotarget Volume 11 Issue 15 reported that the frequency of ERG fusion is variable by race; however, there is limited data available on germline polymorphisms associated with ERG fusion status.

Initial discovery analysis based on SNPs on an Oncoarray SNP chip, showed significant association for SNPs with ERG fusion status.

This study identified SNPs associated with ERG status of Ca P. The findings may contribute towards defining the underlying genetics of ERG positive and ERG negative Ca P... continue reading >>

Oncotarget: PIM and CDK4/6 suppresses both mTOR signaling and Rb phosphorylation


Oncotarget Volume 11, Issue 17 reported that aberrant activation of mitogenic signaling pathways in cancer promotes growth and proliferation of cells by activating mTOR and S6 phosphorylation, and D-cyclin kinases and Rb phosphorylation, respectively.

In this study, the authors showed that the CDK4/6 inhibitor abemaciclib inhibits PIM kinase and S6 phosphorylation in cancer cells and concurrent inhibition of PIM, CDK4, and CDK6 suppresses both S6 and Rb phosphorylation.

Dr. Sean G. Buchanan... continue reading >>

Oncotarget: Molecule inhibits T-cell acute lymphoblastic leukaemia oncogenic interaction


Volume 11, Issue 19 of @Oncotarget reported that a key requirement for the formation of this oncogenic protein-protein interaction is the conformational flexibility of LMO2.

Here the authors identify a small molecule inhibitor of the SCL-LMO2 PPI, which hinders the interaction in vitro through direct binding to LMO2.

Dr. Erika J. Mancini from the School of Life Sciences, Biochemistry Department, University of Sussex, Falmer, Brighton, BN1 9QG, United Kingdom said, "Stem cell leukemia (SCL,... continue reading >>

Renin-angiotensin inhibitors reprogram tumor immune microenvironment: A comprehensive view of the influences on anti-tumor immunity


The cover for issue 84 of Oncotarget features Figure 2, "Renin-angiotensin inhibitors reprogram tumor immune microenvironment," by Zhu, et al.

The mechanisms by which RASi impair tumor growth extend beyond their function of modulating tumor vasculature.

Dr. Dora L. Vallejo-Ardila from the Department of Surgery, Austin Health, at the University of Melbourne, in Melbourne,VIC 3084, Australia said, "The main components of the conventional axis of the renin-angiotensin system, function as an... continue reading >>

Expression of angiopoietin-like 4 fibrinogen-like domain increases the risk of metastases


Volume 11, Number 18 of @Oncotarget reported that using a murine model of brain metastases, The Research Team investigated the roles of nANGPTL4 and cANGPTL4, the two cleaved fragments of ANGPTL4, in the occurrence of brain metastases.

Multivariate analyses found that only breast cancer brain metastases were significantly associated with elevated ANGPTL4 serum concentrations.

On tissue sections, compared to wild-type mice, mice injected with nANGPTL4 cells had significantly larger surface... continue reading >>

A distinct pattern of one-carbon metabolism in invasive breast cancer


Volume 11, Issue 18 of @Oncotarget reported that activation of one-carbon metabolism in tumor cells can sustain oncogenesis while contributing to epigenetic changes and metabolic adaptation during tumor progression.

The authors assessed whether increased one-carbon metabolism activity is a metabolic feature of invasive ductal carcinoma.

Their targeted metabolomics analysis showed distinct metabolomics profiles between IDC and adjacent tissue, where IDC displayed a comparative enrichment of... continue reading >>

Nasal administration of mesenchymal stem cells restores cisplatin-induced cognitive impairment and brain damage in mice


The cover for issue 85 of Oncotarget features Figure 3, "Effect of cisplatin and MSC on brain functional connectivity," by Chiu, et al.

Mice were treated with two cycles of cisplatin followed by nasal administration of MSC. Nasal MSC treatment fully reversed these cognitive deficits in males and females. Nasal administration of MSC did not interfere with the peripheral anti-tumor effect of cisplatin. Nasal administration of MSC may represent a powerful, non-invasive, and safe regenerative... continue reading >>

Nutlin-3a suppresses poly polymerase 1 in a human breast cancer cell line


Volume 11, Number 18 of @Oncotarget reported that the authors previously reported that nutlin-3 induced PARP1 degradation in a p53-dependent manner in mouse fibroblasts, suggesting nutlin-3a may be a PARP1 suppressor.

Short-term nutlin-3a treatment elevated the levels of PARylated PARP1, suggesting nutlin-3a promoted PARylation of PARP1, thereby inducing its proteasomal degradation.

This study revealed that nutlin-3a is a PARP1 suppressor that induces PARP1 proteasomal degradation by binding... continue reading >>

Loss of TXNIP enhances peritoneal metastasis and can be abrogated by dual TORC1/2 inhibition


The cover for issue 86 of Oncotarget features Figure 6, "Schematic representation of the duality of TXNIP function as it pertains to peritoneal carcinomatosis/sarcomatosis," by Spaeth-Cook, et al.

Outliers were validated in The Cancer Genome Atlas and an ovarian tissue microarray and by modulation in ovarian cancer models in vitro and in peritoneal xenograft models.

Dr. James L. Chen from the Department of Biomedical Informatics, Division of Bioinformatics & the Department of Internal... continue reading >>

Proteomic analysis identifies signatures associated w/ survival in breast cancer patients


The cover for issue 17 of @Oncotarget features Figure 8, "Survival probability according to the expression of IGF1R mRNA and an additional gene," by Sinai-Livne, et al.

READ MORE: While this paradigm is based on well-established biological facts, including the potent anti-apoptotic and cell survival capabilities of the receptor, most Phase III clinical trials designed to target the IGF1R led to disappointing results.

Of clinical relevance, these analyses indicate that high IGF1R baseline... continue reading >>

Expression of Nrf2 and NF-κB transcription factors in breast cancer & breast fibroadenoma


Volume 11, Number 18 of @Oncotarget reported that cancer and fibroadenoma are the most common breast tumors in women of reproductive age.

However, few studies have analyzed these markers in breast cancer and fibroadenoma in women of reproductive age.

Nrf2 and NF- B expression was significantly higher in breast cancer than in fibroadenoma, in addition to having a greater association with more aggressive tumors.

Dr. Benedito Borges da Silva from Postgraduate Program, Northeast Biotechnology... continue reading >>

Clinical implications of chromatin accessibility in human cancers


Volume 11, Issue 18 of @Oncotarget Clinical implications of chromatin accessibility assessed by ATAC-seq profiling in human cancers especially in a large patient cohort is largely unknown.

In this study, the authors analyzed ATAC-seq data in 404 cancer patients from the Cancer Genome Atlas, representing the largest cancer patient cohort with ATAC-seq data, and correlated chromatin accessibility with patient demographics, tumor histology, molecular subtypes, and survival.

Chromatin... continue reading >>

Prognostic and predictive factors associated with ipilimumab-related adverse events


Volume 11, Number 16 of @Oncotarget reported that the prevalence of ipilimumab-related toxicity was associated with the patient to the duration of ipilimumab exposure, radiographic responses, progression-free survival, and overall survival.

The number of agents combined with ipilimumab on trial was associated with the average number of grade 3/4 toxicities ipilimumab monotherapy versus ipilimumab + 1 agent versus ipilimumab + 2 agents.

A number of low-grade toxicities were associated with... continue reading >>

Graded expression of microRNA-371a-3p in tumor tissues, contralateral testes, and in serum


Volume 11, Number 16 of @Oncotarget reported that Mi R-levels in GCT tissue are 399-fold higher than in contralateral testicular tissue and 5843-fold higher than in non-testicular tissue.

Low expression is also found in normal testicular tissue but not in non-testicular tissue.

Mi R-371a-3p levels in tissue and serum correlate significantly.

Expression levels of mi R-371a-3p were concurrently measured in tissues of GCT, contralateral testes, and in serum with real-time PCR.

Dr. Gazanfer... continue reading >>

Characterization of GRK5 as a novel regulator of rhabdomyosarcoma tumor cell growth and self-renewal


Volume 11, Number 16 of @Oncotarget reported that through functional assays in vitro and in vivo, the authors show that GRK5 regulates cell cycle in a kinase-independent manner to promote RMS tumor cell growth.

Treatment of human RMS xenografts in mice with CCG-215022, a GRK5-selective inhibitor, results in reduced tumor growth and self-renewal in both major subtypes of RMS. GRK5 represents a novel therapeutic target for the treatment of RMS.

Dr. Eleanor Y. Chen from The Department of... continue reading >>

Oncotarget: A chance for targeting cancer stem cells in human non-small cell lung cancer?


Oncotarget recently published "CD44+/EPCAM+ cells detect a subpopulation of ALDHhigh cells in human non-small cell lung cancer: A chance for targeting cancer stem cells?" which reported that a comparison between ALDH high cells and CD44 cells have been previously described with no significant correlation.

This cross-sectional study analyzed the expression of ALDHhigh/low cells and the positivity for CD44 and epithelium cell adhesion molecule antigens in surgical lung cancer tissues.

There was ... continue reading >>

MicroRNA expression associated with metastasis & survival in patients with uveal melanoma


Volume 11, Number 16 of @Oncotarget reported that multiple survival analyses were done, using the Cox proportional hazards model, to evaluate interactions between mi RNA expression, metastasis, and OS. Of the 22 mi RNAs differentially expressed with respect to metastasis, 21 were significantly associated with OS. The expression of multiple mi RNAs was significantly associated with metastasis and overall survival in patients with UM.

Dr. John J. Wallbillich from The Center for Biotechnology and ... continue reading >>

Oncotarget Molecular imaging reveals biodistribution of P-cadherin LP-DART bispecific


Oncotarget Volume 11 Issue 15 reported that P-cadherin-LP-DART is a bispecific antibody targeting P-cadherin expressed on the tumor cells and CD3 on the T-cells.

P-cadherin-LP-DART accumulation in the tumor was 20-25 fold higher compared to Control-LP-DART demonstrating the targeting specificity.

Imaging after engraftment of CV815 labeled T-cells showed P-cadherin-LP-DART mediated T-cell trafficking in tumors.

Dr. Anand Giddabasappa from Global Science & Technology (GST) – Comparative... continue reading >>

Combinations of paclitaxel and withaferin A against human non-small cell lung cancer


Oncotarget Volume 11 Issue 16 showed that the sensitivity of H1299 and A549 cells to concomitant treatment with PAC and WFA was greater than that of either PAC or WFA alone.

Interestingly, the synergism of PAC and WFA was not schedule-dependent but was enhanced when cells were pretreated with WFA indicating a chemo-sensitizing effect.

Taken together, the results demonstrate the efficacy of WFA alone or alongside PAC on NSCLC cells and provide a strong rationale for further detailed testing in ... continue reading >>

Pitfalls on sample preparation for ex vivo imaging of resected cancer tissue using enzyme-activatable fluorescent probes


The cover for issue 89 of Oncotarget features Figure 4, "Fluorescence images after the probe is sprayed on the extracted tumor," by Mochida, et al.

While a variety of fluorescent probes have been proposed for this task, small molecule enzyme-activatable fluorescent probes are ideal for this application.

In this study two enzyme activatable probes, γ-glutamylhydroxymethyl rhodamine green that reacted with γ-glutamyltransferase and SPiDER-βGal that reacted with β-galactosidase, were employed to ... continue reading >>

Oncotarget A phase II study of axalimogene filolisbac for patients with anal cancer


Oncotarget Volume 11 Issue 15 reported that The Authors conducted this single-arm, multicenter, phase 2 trial in patients with persistent/recurrent, loco-regional or metastatic SCCA. Thirty-six patients were treated; 29 patients were evaluable for response.

One patient had a prolonged partial response.

Grade 3 adverse events were noted in 10 patients, with the majority being cytokine-release symptoms; one grade 4 adverse event was noted.

Dr. Cathy Eng from The MD Anderson Cancer Center,... continue reading >>

Human papillomavirus confers radiosensitivity in oropharyngeal cancer cells


The cover for issue 16 of Oncotarget features Figure 6, "Radiation-induced DNA damage measured by γ-H2AX foci formation at a specified time point after 10 Gy irradiation," by Zhang, et al.

HPV-negative UM-SCC4 with and without transfection of HPV E6 oncoprotein, HPV-negative UPCI-SCC-089, and HPV-positive UPCI-SCC-099 cell lines were used in this study.

The survival fraction after 10 Gy was significantly lower for the HPV-positive SCC-099 cells than for the HPV-negative cells.

In contrast,... continue reading >>

Oncotarget Superior cancer preventive efficacy of low versus high dose of mTOR inhibitor


Oncotarget Volume 11 Issue 15 reported that since mTOR pathway regulation involves multiple feedback mechanisms that may be differentially activated depending on the degree of mTOR inhibition, we investigated whether rapamycin dosing could be adjusted to achieve chemopreventive efficacy without side effects.

While both doses tested were equally effective in suppressing the proliferation of prostate epithelial cells, a higher dose resulted in the activation of feedback circuits that reduced the ... continue reading >>

Oncotarget Co-activation of Sonic Hedgehog and epidermal growth factor


Oncotarget Volume 11 Issue 15 reported that The Research Team re-analyzed publicly available data to study how SHH and EGF cooperate to affect the dynamic activity of the gene population.

They also identified cross-talk genes that exhibited expression profiles dissimilar to that seen under SHH or EGF stimulation alone.

These unique cross-talk patterns were validated in a cell culture model.

These cross-talk genes identified here may serve as valuable markers to study or test for EGF... continue reading >>

Oncotarget Novel plant microRNAs do not show cross-kingdom regulation of pancreatic cancer


Oncotarget Volume 11 Issue 14 reported that the most promising candidates were the already known micro RNA sequence bra-mi R156g-5p and the new sequence Myseq-330, both with predicted human target genes related to apoptosis.

These data demonstrate that broccoletti sprouts contain micro RNA sequences with putative binding sites in human genes, but the sequences evaluated here did not affect cancer growth.

Dr. Ingrid Herr from the Molecular OncoSurgery Group, Section of Surgical Research,... continue reading >>

Oncotarget Pirfenidone anti-fibrotic effects are partially mediated


Oncotarget Volume 11 Issue 15 reported that additionally, immunoprecipitation and immunofluorescence studies in ATII cells and lung fibroblasts showed that pirfenidone inhibited the formation and nuclear translocation of the transcriptional fibrotic TGF- 1-induced phospho-SMAD3/MUC1-CT/active- -catenin complex, and consequently the SMAD-binding element activation.

This study provided also evidence of the inhibitory effect of pirfenidone on the TGF- 1-induced ATII to mesenchymal and fibroblast... continue reading >>

Oncotarget First-in-human study of anticancer immunotherapy drug candidate mobilan


Oncotarget Volume 11 Issue 14 reported that in mice, Mobilan injection into prostate tumors resulted in autocrine TLR5 signaling, immune system activation, and suppression of tumor growth and metastasis.

Here the Research Team reports a first-in-human placebo-controlled clinical study of Mobilan aimed at evaluating safety, tolerability, pharmacokinetics, and pharmacodynamics of a single intra-prostate injection of Mobilan in early-stage prostate cancer patients.

Dr. Vasily I. Kazey from... continue reading >>

Oncotarget Zebrafish B cell acute lymphoblastic leukemia: new findings in an old model


Oncotarget Volume 11 Issue 15 reported that several zebrafish T-ALL models have been reported, but until recently, robust D. rerio B-ALL models were not described.

Here, the Research Team has shown new B-ALL findings in one of these models, fish expressing transgenic human MYC.

They describe B-ALL incidence in a large cohort of hMYC fish, and show B-ALL in two new lines where T-ALL does not interfere with B-ALL detection.

Dr. J. Kimble Frazer from the Department of Cell Biology and the... continue reading >>

Oncotarget A mutation-specific, single-arm, phase 2 study of dovitinib


Oncotarget Volume 11 Issue 14 reported that of 80 patients enrolled, common tumors included gastrointestinal stromal tumors, colorectal cancer, and ovarian cancer.

The most common treatment-related adverse events were fatigue, diarrhea, nausea, and vomiting.

In this heterogeneous patient population, the safety profile was acceptable for dovitinib therapy.

A subset of patients with RTK pathway-activated tumors experienced clinical benefit.

Dr. Matthew H. Taylor from the Division of... continue reading >>

Oncotarget Targeted alpha therapy using astatine (211At)-labeled phenylalanine


Oncotarget Volume 11 Issue 15 reported that C6 glioma, U-87MG, and GL261 cell lines were subjected to a cellular 211At-PA uptake analysis that included an evaluation of the uptake inhibition by the system L amino acid transporter inhibitor 2-aminobicyclo- -heptane-2-carboxylic acid.

BCH significantly inhibited para-211At-PA uptake in C6 glioma, U-87MG, and GL261 cells compared to baseline, suggesting an uptake contribution by system L amino acid transporters.

Dr. Tadashi Watabe from The... continue reading >>

Oncotarget Exosome mediated miR-155 delivery confers cisplatin chemoresistance in oral cancer cells via epithelial-mesenchymal transition


Oncotarget Volume 11 Issue 13 reported that in the present study, we document for the first time the critical role of exosomes in mediating increments in mi R-155 expression in OSCC cells that have acquired cisplatin resistance.

Importantly, exosomal transfer from cis Res to the cisplatin sensitive cells was found to confer significant mi R-155 induction in the recipient cis Sens cells.

Restoration of mi R-155 expression in cis Sens cells following mi R-155 mimics treatment led to epithelial... continue reading >>

Oncotarget Does breast carcinoma belong to the Lynch syndrome tumor spectrum?


Oncotarget Volume 11 Issue 14 reported that somatic mutational profiles of 578 cancer-relevant genes were determined for LS-breast cancer, non-carrier breast cancer, LS-ovarian cancer, and LS-colorectal cancer from the National LS Registry of Finland.

LS-BCs that were pMMR resembled NC-BCs with respect to somatic mutational loads, whereas mutational signatures shared features of dMMR LS-BC, LS-OC, and LS-CRC. Epigenetic regulatory genes were significantly enriched as mutational targets in... continue reading >>

Inhibition of SYK kinase does not confer a pro-proliferative or pro-invasive phenotype in breast epithelium or breast cancer cells


The cover for issue 14 of Oncotarget features Figure 5, "Effect of 15-day incubation of BI 1002494 on T-47D breast cancer cells cultivated in alginate capsules in a bioreactor," by Lamb, et al.

SYK has been reported to possess both tumour promoter and repressor activities and deletion has been linked to a pro-proliferative / pro-invasive phenotype in breast tumours.

An in silico genetic analysis in breast tumour samples revealed no evidence that SYK has a typical tumour suppressor gene... continue reading >>

Oncotarget Expression and serum levels of the neural cell adhesion molecule


Oncotarget Volume 11, Issue 13 reported that expression of CHL1 was analyzed in primary tumor specimens and metastases.

CHL1 expression was detected in GIST specimens.

Local CHL1 expression and serum CHL1 levels show a reverse prognostic behavior, highlighting the relevance of proteolytic shedding of the molecule.

Dr. Karl-Frederick Karstens from the Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg Eppendor, Hamburg, Germany said, "Gastrointestinal... continue reading >>

Oncotarget Transcriptional regulation of HSPB1 by Friend leukemia integration-1 factor


Oncotarget Volume 11, Issue 13 RNAseq analysis identified HSPB1 as a prominent upregulated HSP in GBM and in radiation resistant/temozolomide resistant GBM. Overexpression of Fli-1 in GBM promotes resistance, whereas Fli-1 knockdown in radio/TMZR GBM cells suppresses resistance.

This study uncovers Fli-1 as a potential therapeutic target for combating radiation and temozolomide resistance in GBM.

Dr. Mahitosh Mandal from the School of Medical Science and Technology, Indian Institute of... continue reading >>

Oncotarget Investigation of the role of VHL-HIF signaling in DNA repair and apoptosis


Oncotarget Volume 11, Issue 13 reported that although HIF promotes the progression of cc RCC, the precise mechanism by which the loss of VHL leads to tumor initiation remains unclear.

This research team exploited two zebrafish vhl mutants, vhl and vll, and Tg i144 fish to identify crucial functions of Vhl in tumor initiation.

Dr. Fredericus J. van Eeden from the Bateson Centre/BMS, Firth Court, University of Sheffield, Sheffield S10 2TN, UK said "In humans, mutations in the pVHL protein, a... continue reading >>

Oncotarget The value of lncRNA FENDRR and FOXF1 as a prognostic factor for survival


Oncotarget Volume 11, Issue 13 reported that the present study aimed to define the clinic pathological significance of the long-non-coding RNA FENDRR in lung adenocarcinomas.

Dr. Pedro P. Medina from the Department of Biochemistry and Molecular Biology I, as well as the Centre for Genomics and Oncological Research, PTS Granada, Centro Pfizer - Universidad de Granada - Junta de Andalucía de Genómica e Investigación Oncológica (GENYO), Granada, Spain said "Lung cancer is the most lethal cancer... continue reading >>

Oncotarget Synergistic cytotoxic activity of cannabinoids from cannabis sativa


The cover for issue 13 of Oncotarget features Figure 5, "Hierarchical clustering and Venn diagram of genes significantly differentially expressed genes in My-La and HuT-78 cells treated with S4, S5 or the S4+S5 synergistic combination," by Mazuz, et al.

This study aimed to identify active compounds from whole cannabis extracts and their synergistic mixtures, and to assess respective cytotoxic activity against CTCL cells.

Active cannabis compounds presenting high cytotoxic activity on My-La... continue reading >>

Oncotarget Loss of p16 and high Ki67 labeling index is associated with poor outcome


Oncotarget Volume 11, Issue 12 reported that the p16 tumor suppressor is coded by CDKN2A and plays an important role during carcinogenesis and tumor progression in numerous tumor entities.

P16 positivity was found in 30.2% of AC and 13.9% of SCC and CDKN2A deletion in 32.1% of AC and 33.5% of SCC. In AC Ki67 positivity was associated with high tumor stage, presence of lymph node metastasis, high UICC stage and poor grading.

Dr. Nathaniel Melling from the Department of General, Visceral and... continue reading >>

Oncotarget Cancer associated fibroblasts confer shear resistance to circulating tumor cell


Oncotarget Volume 11, Issue 12 reported that the observation that Cancer associated fibroblasts (CAFs) disseminate with Circulating Tumor Cells (CTCs) prompts the examination of the role of CAFs in CTC survival under physiological shear stress during the dissemination process using a clinically relevant, three-dimensional co-culture model.

In this study, the research team found that reactive CAFs induce shear resistance to prostate tumor cells via intercellular contact and soluble derived... continue reading >>

Oncotarget Characterization of iPS87, a prostate cancer stem cell-like cell line


Oncotarget Volume 11, Issue 12 reported outside its natural niche, the cultured prostate cancer stem cells lost their tumor-inducing capability and stem cell marker expression after approximately 8 transfers at a 1:3 split ratio.

To characterize the iPS87 cell line, cells were stained with antibodies to various markers of stem cells including: ALDH7A1, LGR5, Oct4, Nanog, Sox2, Androgen Receptor, and Retinoid X Receptor.

This research thus characterizes the iPS87 cell line as a... continue reading >>

Oncotarget Roscovitine enhances all-trans retinoic acid (ATRA)-induced nuclear enrichment


Oncotarget Volume 11, Issue 12 reported that using the HL-60 human non-APL AML model where ATRA causes nuclear enrichment of c-Raf that drives differentiation/G0-arrest, the research team now observe that roscovitine enhanced nuclear enrichment of certain traditionally cytoplasmic signaling molecules and enhanced differentiation and cell cycle arrest.

ATRA-induced loss of pS608RB with cell cycle arrest was associated with loss of RB-sequestered c-Raf, thereby coupling cell cycle arrest and... continue reading >>

Oncotarget hPCL3S promotes proliferation and migration of androgen-independent prostate cancer cells


The cover for issue 12 of Oncotarget features Figure 11, "Global analyses of the RNA-Seq data of LNCaP empty vector and LNCaP cells overexpressing hPCL3S (Clone 12)" by Abdelfettah, et al.

These proteins contain a TUDOR domain binding H3K36me3, two PHD domains and a Winged-helix domain involved in GC-rich DNA binding.

The human PCL3 locus encodes the full-length hPCL3L protein and a shorter isoform, hPCL3S containing the TUDOR and PHD1 domains only.

A mutant hPCL3S unable to bind H3K36me3... continue reading >>

Oncotarget Anticancer activity of 2'-hydroxyflavanone towards lung cancer


Oncotarget Volume 9, Issue 90 of features Figure 4, "Docking of 2HF, DNPSG and ATP to RLIP76," by Awasthi, et al.

The researchers studied 2HF in small cell and non-small cell lung cancer cell lines for sensitivity to 2HF antineoplastic activity and to determine the role of the GS-E transporter Rlip in the mechanism of action of 2HF. Binding of Rlip to 2HF was evident from successful purification of Rlip by 2HF affinity chromatography.

Results of in-vivo nude mouse xenograft studies of SCLC... continue reading >>

Oncotarget Acute promyelocytic leukemia (APL): a review of the literature


Oncotarget Volume 11, Issue 11 reported that relapsed APL, particularly in the high-risk subset of patients, remains an important clinical problem.

The probability of relapse is significantly higher in the high-risk subset of patients undergoing treatment for APL; overall approximately 10-20% of APL patients relapse regardless of their risk stratification.

Alternative agents and approaches considering these clinical outcomes are needed to address ATO resistance as well as the relapse rate in... continue reading >>

Oncotarget Early prediction of resistance to tyrosine kinase inhibitors by plasma monitoring of EGFR mutations in NSCLC: a new algorithm for patient selection and personalized treatment


Oncotarget Volume 11, Issue 11 reported that at clinical progression, 64 EGFR T790M plasma positive patients were subjected to second line-treatment with osimertinib and strictly monitored during the first month of therapy.

Plasma analysis by the EGFR Cobas test showed in 57 cases a substantial decrease in the levels of the sensitizing EGFR mutant allele, down to a not detectable value.

The research team's data indicate that plasma monitoring by a simple RT-PCR-based EGFR mutation test in the ... continue reading >>

Oncotarget | DOT1L inhibition is lethal for multiple myeloma due to perturbation of the endoplasmic reticulum stress pathway


Oncotarget Volume 11, Issue 11 reported that in order to understand the molecular mechanism of the dependency in MM, the research team examined gene expression changes upon DOT1L inhibition in sensitive and insensitive cell lines and discovered that genes belonging to the endoplasmic reticulum stress pathway and protein synthesis machinery were specifically suppressed in sensitive cells.

Whole-genome CRISPR screens in the presence or absence of a DOT1L inhibitor revealed that concomitant... continue reading >>

Oncotarget | Quizartinib, a selective FLT3 inhibitor, maintains antileukemic activity in preclinical models of RAS-mediated midostaurin-resistant acute myeloid leukemia cells


Oncotarget Volume 11, Issue 11 reported that in this preclinical study, we characterized the binding affinity and selectivity of quizartinib, a small-molecule inhibitor of FLT3, and AC886, the active metabolite of quizartinib, compared with those of other FLT3 inhibitors.

Dr. Takeshi Isoyama from Daiichi Sankyo Co., Ltd. said, "FMS like tyrosine kinase 3 (FLT3) is a receptor tyrosine kinase expressed by acute myeloid leukemia (AML) cells in 70% to 90% of patients."

"FMS like tyrosine... continue reading >>

Oncotarget | Targeting PI3Kβ alone and in combination with chemotherapy or immunotherapy in tumors with PTEN loss


The cover for issue 11 of Oncotarget features Figure 6, "Effects of AZD8186 in combination with anti-PD1 on syngeneic models," by Owusu-Brackett, et al.

In vitro cell viability assay and immunoblotting demonstrated that PTEN loss was significantly correlated with AZD8186 sensitivity in triple-negative breast cancer cell lines.

AZD8186 in combination with paclitaxel, eribulin had synergistic effects on growth inhibition in PTEN loss cells.

AZD8186 significantly enhanced the antitumor efficacy ... continue reading >>

Intratumoral CD56bright natural killer cells are associated with improved survival in bladder cancer


The cover for issue 92 of Oncotarget features Figure 4, "Intratumoral CD56bright NK cells are more functional than CD56dim NK cells and correlate with survival in bladder cancer," by Mukherjee, et al.

Fluorescence-activated cell sorting of intratumoral lymphocytes isolated CD56 NK cell subsets were used for examination of function, including cytokine production and in vitro cytotoxicity. NK cells predominated among bladder intratumoral lymphocytes. Bladder intratumoral CD56bright NK cells are... continue reading >>

Oncotarget | Clofarabine/busulfan-based reduced intensity conditioning regimens provides very good survivals in acute myeloid leukemia patients in complete remission at transplant: a retrospective study on behalf of the SFGM-TC


The cover for issue 93 of Oncotarget features Figure 2, "Comparison of overall survival (OS) and leukemia-free survival (LFS) between CloB2A1 and CloB2A2 sub-groups," by Le Bourgeois, et al.

Clo B2A2/A1 RIC regimen provides very good results for AML patients allografted in CR and could be retained as a new RIC platform for these patients.

This was a retrospective study including all patients who received a clofarabine/busulfan based RIC allo-SCT for myeloid malignancies and reported within... continue reading >>

Oncotarget | Genomic loss of heterozygosity and survival in the REAL3 trial


The cover for issue 94 of Oncotarget features Figure 6, "Progression free survival in LOH-high and LOH-low groups with operated patients censored at time of potentially curative surgery," by Smyth, et al.

Diagnostic biopsy DNA from patients treated in the REAL3 trial was sequenced using the Foundation Medicine T5 next-generation sequencing assay. A cut-off of 21% genomic LOH defined an LOH-high subgroup who had median overall survival of 18.3 months versus 11m for the LOH-low group.

HRD... continue reading >>

Oncotarget | Prognostic and predictive factors in pancreatic cancer


Oncotarget Volume 11, Issue 10 reported that there are not standardized predictive biomarkers able to identify patients who benefit most from treatments.

The aim of this review is to provide an overview of prognostic and predictive markers used in clinical practice and to explore the most promising fields of research in terms of treatment selection and tailored therapy in pancreatic cancer.

Dr. Fabrizio Citarella from the Department of Medical Oncology, University Campus Bio-Medico, Rome... continue reading >>

Oncotarget | MicroRNA (miR) dysregulation during Helicobacter pylori-induced gastric inflammation and cancer development: critical importance of miR-155


Oncotarget Volume 11, Issue 10 reported that dysregulation of noncoding micro RNA molecules has been associated with immune cell activation in the context of Helicobacter pylori-induced gastric inflammation as well as carcinogenesis, but also with downregulation of mismatch repair genes, and may interfere with immune checkpoint proteins that lead to the overexpression of antigens on gastric tumor cells.

Among the many micro RNAs involved in gastric inflammation, adenocarcinoma development and... continue reading >>

Oncotarget | DNA methylation of MMPs and TIMPs in atherothrombosis process in carotid plaques and blood tissues


Oncotarget Volume 11, Issue 10 reported that the statistically associated Cp G sites were analyzed in blood samples from two separate atherothrombotic stroke cohorts, ischemic stroke-cohort 1: 37 atherothrombotic patients and 6 controls, ischemic stroke-cohort 2: 80 atherothrombotic patients and 184 controls.

The results suggest different DNAm status of MMP24 between stable and unstable atherothrombotic carotid plaques, and between atherothrombotic stroke and controls in blood samples.

Dr.... continue reading >>

Oncotarget | A microRNA-based signature predicts local-regional failure and overall survival after pancreatic cancer resection


The cover for issue 10 of Oncotarget features Figure 3, "Overall survival (OS) for high (red) versus low (black) risk groups in the (A) OSU, (B) TCGA, and (C) SNU resected cohorts," by Wolfe, et al.

Digital mi RNA expression profiling was performed and risk scores were calculated based on the expression levels of the four most significantly correlated mi RNAs and dichotomized about the median to detect correlations between risk group, LRR and overall survival.

On multivariable analysis, the... continue reading >>

Oncotarget | Tubulin couples death receptor 5 to regulate apoptosis


The cover for issue 95 of Oncotarget features Figure 8, "Tubulin/microtubule regulation of DR5 mediated apoptosis," by Twomey, et al.

Activation of death receptor 5 to induce apoptosis in cancer cells is an attractive strategy for cancer therapy. Together, our results link the tubulin/microtubule network to the stringent regulation of DR5 mediated apoptosis, which could lead to potential therapeutic strategies to enhance cancer therapy efficacy.

Dr. Baolin Zhang from the Office of... continue reading >>

Oncotarget | Glypican-1 in human glioblastoma: implications in tumorigenesis and chemotherapy


Oncotarget Volume 11, Issue 9 reported that this study aimed to investigate how glypican-1 influences the tumoral profile of human glioblastoma using in vitro cell line models.

Therefore, we present evidence not only to support facts that glypican-1 is an elementary macromolecule in glioblastoma tumoral microenvironment but also to introduce this proteoglycan as a promising therapeutic target for this lethal tumor.

Dr. Leny Toma from the Department of Biochemistry, Universidade Federal de São... continue reading >>

Oncotarget | Prolyl 4-hydroxylase alpha 1 protein expression risk-stratifies early stage colorectal cancer


Oncotarget Volume 11, Issue 8 reported Independent validation cohorts of 599 cases of early-stage CRC and 91 cases of late-stage CRC were examined.

Multivariate and univariate survival analyses revealed that high expression of P4HA1 protein was an independent poor prognostic marker for patients with early-stage CRC, especially of the microsatellite stable subtype.

Dr. Michael H. Roehrl from the Department of Pathology, Memorial Sloan Kettering Cancer Center as well as the Human Oncology and... continue reading >>

Oncotarget | Analysis of mutations in primary and metastatic synovial sarcoma


The cover for issue 96 of Oncotarget features Figure 5, "Analysis of the effects of metastatic synovial sarcoma-associated ADAM17 mutations using cell migration assay," by Xing, et al.

To explore the possibilities to investigate metastatic mechanisms of synovial sarcoma, the research team carried out the first genome-wide search for potential genetic biomarkers and drivers associated with metastasis by comparative mutational profiling of 18 synovial sarcoma samples isolated from four patients... continue reading >>

Oncotarget | Phase I/II clinical trial of the targeted chemotherapeutic drug, folate-tubulysin, in dogs with naturally-occurring invasive urothelial carcinoma


The cover for issue 97 of Oncotarget features Figure 4, "Representative examples of FR expression detected on canine kidney," by Szigetvari, et al.

Experimental Design: A 3+3 dose escalation study of EC0531 was performed in dogs with iUC expressing high levels of FRs.

Unlike human neutrophils, canine neutrophils were found to express FRs, which contributes to the neutropenia at higher doses of EC0531 in dogs.

It is likely that humans will tolerate higher, potentially more effective doses of... continue reading >>



Wednesday, March 4, 10:00 am ET
30-Minute Webinar with Q&A

Register now: https://webinar-register.net/webinars/ij/registration_200304.php

To be an effective and successful research scientist, you need to know how to overcome the challenges involved in conveying information to an audience beyond your institution–or what NIH likes to call "demonstrating societal influence."

To make the right decisions regarding your ... continue reading >>

Oncotarget | The transcription factor CUX1 negatively regulates invasion


Oncotarget Volume 11, Issue 9 reported CUX1 expression was increased in androgen-independent cells compared to androgen-sensitive cells.

This observed difference in invasion capacity is not E-cadherin mediated, as CUX1 knockdown increases the expression of E-cadherin in both cell lines with no inter-cell line difference.

Rather than a simple presence or absence of CUX1, the relative balance of CUX1 isoforms and their interplay may be a significant factor in the functional role of CUX1 in CRPC.... continue reading >>

Oncotarget | Genetic biomarkers predict response to dual BCL-2 and MCL-1 targeting in acute myeloid leukaemia cells


The cover for issue 102 of Oncotarget features Figure 9, "Apoptotic resistance to Venetoclax in FLT3 mutated primary samples can be reversed when combined with S63845," by Grundy, et al.

Acute myeloid leukaemia cells often up-regulate pro-survival members of the BCL-2 protein family, such as BCL-2 and MCL-1, to avoid apoptosis.

The research team treated MV4-11 cells and primary AML samples for 4 hours with Venetoclax, S63845 or the combination.

The combination of Venetoclax and S63845... continue reading >>

Oncotarget | Molecular subtypes of triple-negative breast cancer in women of different race and ethnicity


Oncotarget Volume 10, Issue 2 reports that Hispanics had a significantly higher proportion of basal-like immunosuppressed (BLIS), whereas Asians had a lower proportion of BLIS and a higher proportion of luminal androgen receptor (LAR) compared to the average proportion across all groups.

Determining subtypes of Triple Negative Breast Cance (TNBC) facilitates understanding of the heterogeneity of the TNBCs and provides a foundation for developing subtype-specific therapies and better predictors ... continue reading >>

Oncotarget | Inducible knock-out of BCL6 in lymphoma cells results in tumor stasis


The cover for issue 9 of Oncotarget features Figure 6, "BCL6 knock-out in a DLBCL xenograft induces tumor stasis," by Schlager, et al.

Read more: An oncogenic role of BCL6 in the initiation of DLBCL has been shown as the constitutive expression of BCL6 in mice recapitulates the pathogenesis of human DLBCL. Conditional BCL6 deletion in established DLBCL tumors in vivo induced a significant tumor growth inhibition with initial tumor stasis followed by slow tumor growth kinetics.

Dr. Manfred... continue reading >>

Oncotarget | The oral tubulin-binder BAL101553 is associated with inhibition


Oncotarget Volume 11, Issue 8 reported that BAL101553, a prodrug of BAL27862, is a novel small molecule tubulin-binding agent, promoting tumor cell death through spindle assembly checkpoint activation, which is currently in Phase 1/2a in advanced solid tumor patients including GBM. This study aimed to evaluate long-term daily oral BAL101553 treatment of mice orthotopically grafted with GBM CSLCs according to EB1 expression-level and to decipher its mechanism of action on GBM stem cells.

Altoget... continue reading >>

Oncotarget | Payload of T-DM1 binds to cell surface cytoskeleton-associated protein 5 to mediate cytotoxicity of hepatocytes


Oncotarget Volume 9, Issue 98 reports upon binding to CKAP5, T-DM1 causes cell membrane damage and leads to calcium influx into the cells, resulting in disorganized microtubule network and apoptosis.

While binding of T-DM1 with HER2 is critical for killing HER2-positive tumor cells, the research team's data suggested that cytotoxicity induced by T-DM1 interaction with CKAP5 may preferentially damage normal cells/tissues where HER2 expression is low or missing to cause off-target toxicity.

Dr. ... continue reading >>

Oncotarget | Subcellular localization of FANCD2 is associated with survival in ovarian carcinoma


Oncotarget Volume 11 Issue 8 reported Nuclear and cytoplasmic localization of FANCD2 was observed in OSEs from both normal and ovarian cancer patients.

Patients with cytoplasmic localization of FANCD2 experienced significantly longer median survival time, versus patients without cytoplasmic localization of FANCD2.

The authors results suggest that the presence of cytoplasmic FANCD2 modulates FANCD2 activity resulting in better survival outcome in ovarian cancer patients.

Dr. Tanja Pejovic... continue reading >>

Oncotarget | SLC25A32 sustains cancer cell proliferation by regulating flavin adenine nucleotide (FAD) metabolism


Oncotarget Volume 11 Issue 8 reported that while it is known that cancer cells require one-carbon and FAD-dependent mitochondrial metabolism to sustain cell proliferation, the role of SLC25A32 in cancer cell growth remains unexplored.

Si RNA-mediated knock-down and CRISPR-mediated knock-out of SLC25A32 in cancer cells of different origins, resulted in the identification of cell lines sensitive and resistant to SLC25A32 inhibition.

Treatment of cells with the FAD precursor riboflavin and with... continue reading >>

Oncotarget | Increased PD-L1 expression in radioresistant HNSCC cell lines after irradiation affects cell proliferation due to inactivation of GSK-3beta


Oncotarget Volume 10, Issue 5 features Figure 5, "PD-L1 function in RR cell lines," by Schulz, et al.

RR cells showed prolonged survival as well as delayed and diminished apoptosis after irradiation with vimentin expression but no E-cadherin expression, whereas RS cell lines died early and exhibited early apoptosis after irradiation and high vimentin expression.

Moreover, the research team observed a radiation dose dependent increase of total PD-L1 protein expression in RR cell lines up to... continue reading >>

Oncotarget | Both BRCA1-wild type and -mutant triple-negative breast cancers show sensitivity to the NAE inhibitor MLN4924 which is enhanced upon MLN4924 and cisplatin combination treatment


Oncotarget Volume 11 Issue 8 features Figure 8, "MLN4924 treatment induces DNA damage by stabilizing CDT1 and accumulates the cells in S phase which are enhanced by MLN4924/cisplatin co-treatment," by Misra, et al.

Moreover, adding MLN4924 to the standard TNBC chemotherapeutic agent cisplatin increased the DNA damage level, further enhancing the sensitivity.

In vivo, MLN4924 reduced tumor growth in a NOD-SCID mouse xenograft model by inducing DNA damage which was further augmented with the... continue reading >>

Oncotarget | Inhibition of ATM kinase upregulates levels of cell death induced by cannabidiol and γ-irradiation in human glioblastoma cells


Oncotarget Volume 10, Issue 8 features Figure 11, "The viability of TS543 human glioma spheroid cultures following treatments with CBD, ATM inhibitor (ATMi), and γ-irradiation (5 Gy), alone or in combination," by Ivanov, et al.

In this study, the researchers (Drs. Vladimir N. Ivanov and Jinhua Wu, both cancer biologists, Tony J.C.Wang, a leading specialist in radiation oncology for brain tumors, and Tom K. Hei, well-known radiobiologist) increased the cytotoxic effects of the combination of... continue reading >>

Oncotarget | Could a Melanoma Vaccine Provide Significant Protection for Humans Against Skin Cancer in the Future?


Oncotarget Volume 11, Issue 7 reported that although melanoma risk can be minimized with behavioral changes, vaccinating high-risk individuals against melanoma may be the most efficacious preventative method.

Accordingly, using a highly attenuated, double-mutant L. monocytogenes strain expressing a tumor-associated antigen, the researchers obtained significant protection against melanoma in a mouse model.

The Listeria-based vaccine-induced protection through antigen-specific CD8+ T-cells... continue reading >>

Oncotarget | DNA dependent protein kinase (DNA-PK) enhances HIV transcription by promoting RNA polymerase II activity and recruitment of transcription machinery at HIV LTR


Oncotarget Volume 11, Issue 7 | The Research Team has previously reported that DNA-dependent protein kinase facilitates HIV transcription by interacting with the RNA polymerase II complex recruited at HIV LTR.

DNA-PK inhibition/knockdown leads to the severe impairment of HIV replication and reactivation of latent HIV provirus.

Dr. Mudit Tyagi from the Center for Translational Medicine at Thomas Jefferson University, the Division of Infectious Diseases in the Department of Medicine at George... continue reading >>

Oncotarget | Mifamurtide and TAM-like macrophages: effect on proliferation, migration, and differentiation of osteosarcoma cells


Oncotarget Volume 11, Issue 7 | The research team analyzed the effects of Mifamurtide on macrophage polarization and on MG63 proliferation, migration, and differentiation, evaluating the expression of M1/M2 and osteoblast markers and molecules involved in metastasis and proliferation pathways.

Their data suggest that Mifamurtide, switching macrophage polarization towards a TAM-like intermediate M1/M2 phenotype, may modulate the delicate balance between pro-inflammatory and immunomodulatory... continue reading >>

Oncotarget | MAGE-A inhibit apoptosis and promote proliferation in multiple myeloma through regulation of BIM and p21Cip1


Oncotarget Volume 11, Issue 7 reported that to investigate the mechanisms of these oncogenic functions, the researchers performed gene expression profiling of p53 wild-type human myeloma cell lines after MAGE-A knockdown, which identified a set of 201 differentially expressed genes associated with apoptosis, DNA repair, and cell cycle regulation.

Comparative analysis of Co MMpass subjects based on high or low MAGEA3 expression revealed a set of 6748 DEG that also had significant functional... continue reading >>

Oncotarget | A randomized, double-blind trial of F14512, a polyamine-vectorized anticancer drug, compared with etoposide phosphate, in dogs with naturally occurring lymphoma


Oncotarget Volume 11, Issue 7 features Figure 4, "Exploratory biomarkers," by Boyé, et al.

The objective of this study was to compare the safety and antitumor activity of F14512 and etoposide phosphate in dogs with spontaneous non-Hodgkin lymphoma and to investigate the potential benefit of F14512 in P-glycoprotein overexpressing lymphomas.

Subgroup analysis of dogs with Pgp-overexpressing NHL showed a significant improvement in PFS in dogs treated with F14512 compared with etoposide... continue reading >>

Oncotarget | Risk factors for breast cancer brain metastases: a systematic review


Oncotarget Volume 11, Issue 6 reported that A systematic literature search of EMBASE and MEDLINE was conducted to elucidate the current state of knowledge on known and novel prognostic factors associated with 1) the risk for BCBM and 2) the time to brain metastases (TTBM).

Of these, 69 studies reported risk factors of BCBM, 46 factors associated with the TTBM and twenty studies examined variables for both outcomes.

Young age, estrogen receptor negativity, overexpression of human epidermal... continue reading >>

Oncotarget | Identification of biomarkers of immune checkpoint blockade efficacy in recurrent or refractory solid tumor malignancies


Oncotarget Volume 11, Issue 6 reported that multivariate regression analysis including the two variables of tumor mutation burden and ICB, and their interaction term, showed favorable survival associated with ICB, unfavorable survival associated with TMB without ICB treatment, and improved outcome with increasing TMB in ICB treated patients.

Tumor TP53 mutation was associated with worse survival, but these patients still benefited from ICB.

Dr. Russell R. Broaddus from the Department of... continue reading >>

Oncotarget | The interplay of CDK4 and CDK6 in melanoma


Sh RNA knockdown of either CDK4 or CDK6 significantly reduces cell proliferation and impedes their migratory capacity in vitro, which translates into a strong inhibition of tumor growth in xenotransplantation experiments.

CDK6 knockdown in melanoma cell lines impairs VEGF-A expression and reduces the potential stimulation of endothelial cell growth.

Bioinformatic analysis of human melanoma patient data verifies the key role of CDK6 in tumor angiogenesis in melanoma.

Dr. Karoline Kollmann... continue reading >>

Oncotarget | In vitro studies on CNGRC-CPG2 fusion proteins for ligand-directed enzyme prodrug therapy for targeted cancer therapy


Oncotarget Volume 11, Issue 6 reported in a recent research paper that in vitro binding assays of the purified constructs showed that both X-CPG2 and X-CPG2-X bound with high affinity to cancer cells expressing high levels of APN, compared to their binding to cells expressing low levels of APN. Further in vitro studies of the constructs to assess the therapeutic potential of LDEPT were carried out using cells expressing high and low levels of APN.

Dr. Sayed K. Goda from the Cairo University,... continue reading >>

Oncotarget | Systemic oncolytic adenovirus delivered in mesenchymal carrier cells modulate tumor infiltrating immune cells and tumor microenvironment in mice with neuroblastoma


Oncotarget Volume 11, Issue 4: The use of xenografts in immunodeficient mice prevent assessing important clinical aspects of this therapy such as the anti adenovirus immune response or the possible intratumoral immune changes, both of tumor infiltrating leukocytes and of the microenvironment.

However, the presence of circulating anti adenovirus antibodies did not prevent changes detected at the tumor masses: increased infiltration and changes in the quality of immune cells per unit of tumor... continue reading >>

Human insulin modulates α-synuclein aggregation via DAF-2/DAF-16 signalling pathway by antagonising DAF-2 receptor in C. elegans model of Parkinson's disease


The aggregation was increased when DAF-16 was knocked-down independently or along with a co-treatment of human insulin and decreased when DAF-2 was knocked-down independently or along with a co-treatment of Hum INS; whereas Hum INS treatment per se, reduced the aggregation.

The author's results depicted that Hum INS decreases -synuclein aggregation via DAF-2/DAF-16 pathway by acting as an antagonist for the DAF-2 receptor.

Dr. Aamir Nazir from the Division of Neuroscience and Ageing Biology... continue reading >>

Empty SV40 capsids increase survival of septic rats by eliciting numerous host signaling networks that participate in a number of systemic functions


The cover for issue 6 of Oncotarget features Figure 3, "The effect of NCs treatments on routine lab results during disease and recovery progress," by Ben-Nun-Shaul, et al.

Numerous previous attempts to develop therapeutic treatments, directed at discreet targets of the sepsis cascade, could not cope with the complex pathophysiology of sepsis and failed.

Studies in a severe rat sepsis model showed that pre-treatment by NCs led to a dramatic increase in survival, from zero to 75%.

Further... continue reading >>

Oncotarget | Preclinical activity of sacituzumab govitecan (IMMU-132) in uterine and ovarian carcinosarcomas


Oncotarget Volume 11, Issue 5: Trop-2 expression was evaluated in 10 formalin-fixed-paraffined-embedded CS by immunohistochemistry and 9 primary CS cell-lines by flow-cytometry.

One Trop-2 low/negative and two Trop-2 positive cell-lines were tested in cell-viability assays.

Trop-2 positive cell-lines showed higher sensitivity to SG in vitro when compared to Trop-2 low/negative cell lines.

Dr. Alessandro D. Santin from the Department of Obstetrics, Gynecology and Reproductive Sciences at Yale ... continue reading >>

Oncotarget | Calcitriol and non-calcemic vitamin D analogue, 22-oxacalcitriol, attenuate developmental and pathological choroidal vasculature angiogenesis ex vivo and in vivo


Oncotarget Volume 11, Issue 5: Here, the author's aim was to validate the ocular anti-angiogenic activity of biologically active vitamin D, calcitriol, and selected vitamin D analogue, 22-oxacalcitriol.

Calcitriol induced a significant reduction in ex vivo mouse choroidal fragment sprouting.

Viability studies in a human RPE cell line suggested non-calcemic vitamin D analogues including 22-oxacalcitriol have less off-target anti-proliferative activity compared to calcitriol and other analogues.... continue reading >>

Oncotarget | Identification of molecular targets for the targeted treatment of gastric cancer using dasatinib


Oncotarget Volume 11, Issue 5: The expression levels of the identified kinases were investigated on RNA and protein level in 200 classified tumor samples from patients, who had undergone gastrectomy, but had received no treatment.

Levels of FRK, DDR1 and SRC expression on both mRNA and protein levels were significantly higher in metastatic patient samples regardless of the tumor stage, while expression levels of SIK2 correlated with tumor size.

Dr. Raquel Carvalho Montenegro from the Drug... continue reading >>

Oncotarget | Cetuximab is efficient and safe in patients with advanced cutaneous squamous cell carcinoma: a retrospective, multicentre study


Oncotarget Volume 11, Issue 4: Chemotherapy, alone or combined with radiotherapy, is commonly used mostly as palliative treatment; moreover, its poor safety profile limits its use most of the time, especially in elderly patients.

Fifty-eight patients received cetuximab as monotherapy.

The median PFS and OS were 9.7 months and 17.5 months, respectively.

Fifty-one patients experienced toxicity, and 67 adverse events related to cetuximab occurred.

Dr. Henri Montaudié from the Department of... continue reading >>

Oncotarget | Sphingomyelin phosphodiesterase 3 methylation and silencing in oral squamous cell carcinoma results in increased migration and invasion and altered stress response


Oncotarget Volume 11 Issue 5: While lentivirus-induced overexpression of SMPD3 in cell models of oral dysplasia and OSCC did not significantly alter proliferation, it did decrease migration and invasion and increased resistance to the epidermal growth factor receptor inhibitor erlotinib.

These results suggest that SMPD3 downregulation is a common event in OSCC progression and may promote the spread of tumor cells.

Dr. Cathie Garnis from the Department of Integrative Oncology at British... continue reading >>

Nimotuzumab-cisplatin-radiation versus cisplatin-radiation in HPV negative oropharyngeal cancer


Oncotarget Volume 11, Issue 4: In this study, locally advanced head and neck cancer patients undergoing definitive chemoradiation were randomly allocated to weekly cisplatin - radiation {CRT arm} or nimotuzumab -weekly cisplatin -radiation {NCRT arm}.

An interaction test was performed between the study arms and HPV status prior to doing any HPV specific analysis for each of the studied outcomes.

We had 187 HPV negative oropharyngeal cancers, 91 in the CRT arm and 96 in NCRT arm.

The addition ... continue reading >>

Oncotarget | FOXL2 homozygous genotype and chromosome instability are associated with recurrence in adult granulosa cell tumors of the ovary


Oncotarget Volume 11, Issue 4: The present study focused on the influence of the FOXL2 genotype and copy number variations in recurrence by comparing the primary tumor with recurrent lesions in the same patient.

The authors also observed that three recurrent tumors and one primary tumor appeared to be homozygous for the FOXL2 c.402C>G mutation.

Despite the small number of matching primary and recurrent tumors analyzed here, the present study is the first to have shown that the FOXL2... continue reading >>

Oncotarget | Inhibition of fibroblast secreted QSOX1 perturbs extracellular matrix in the tumor microenvironment and decreases tumor growth and metastasis in murine cancer models


Oncotarget Volume 11, Issue 4: Extracellular matrix plays an important role in tumor development and dissemination, but few points of therapeutic intervention targeting ECM of the tumor microenvironment have been exploited to date.

Based on this finding and the increased QSOX1 expression in the stroma of aggressive breast carcinomas, we developed monoclonal antibody inhibitors with the aim of preventing QSOX1 from participating in pro-metastatic ECM remodeling.

Here the authors show that... continue reading >>

Tumor secreted ANGPTL2 facilitates recruitment of neutrophils to the lung to promote lung pre-metastatic niche formation and targeting ANGPTL2 signaling affects metastatic disease


Oncotarget Volume 11, Issue 5: The authors determined that tumor-derived ANGPTL2 stimulates lung epithelial cells, which is essential for primary tumor-induced neutrophil recruitment in lung and subsequent pre-metastatic niche formation.

Lastly, they identified that a p63 isoform, Np63, drives a high level of ANGPTL2 secretion and pharmaceutical inhibition of ANGPTL2 signaling by a non-RGD-based integrin-binding peptide diminished metastatic load in lungs likely due to reduction of the lung... continue reading >>

Overall survival in patients with lung adenocarcinoma harboring "niche" mutations: an observational study


The cover for issue 5 of Oncotarget features Figure 2, "Survival curves in the KRAS, EGFR, and niche mutations cohorts," by Aramini, et al.

Mutations were observed in all genes studied, except c-MET, DDR2, MAP2K1, and RET.

The multivariable analysis showed that:

  1. Niche mutations had higher mortality than EGFR mutations
  2. KRAS mutations had higher mortality than EGFR mutations, and
  3. Niche mutations presented similar mortality to KRAS mutations.

Niche mutations exhibited an increased risk of... continue reading >>

Clostridium perfringens enterotoxin induces claudin-4 to activate YAP in oral squamous cell carcinomas


Oncotarget Volume 11, Issue 4: Treatment of human oral squamous cell carcinoma cell lines HSC3 and HSC4 with Clostridium perfringens enterotoxin, induced CLDN4 nuclear translocation to enhance epithelial-mesenchymal transition, stemness, cell proliferation, and invasive ability.

Moreover, it was revealed that the complex of YAP1, CLDN4, and zona occludens-2 was formed by CPE treatment, further suppressing YAP1 phosphorylation by LATS1 and activating it.

Dr. Yi Luo from the Key Laboratory of... continue reading >>

Anti-carcinoembryonic antigen-related cell adhesion molecule antibody for fluorescence visualization of primary colon cancer and metastases in patient-derived orthotopic xenograft mouse models


Oncotarget Volume 11, Issue 4: The research team's aim was to investigate mAb 6G5j binding characteristics and to validate fluorescence targeting of colorectal tumors and metastases in patient derived orthotopic xenograft models with fluorescently labeled 6G5j.

Nude mice received orthotopic implantation of patient-derived primary colon cancer and patient-derived colon cancer metastases.

Anti-CEACAM antibody 6G5j binds multiple CEACAMs which may lead to improved detection of tumor margins for... continue reading >>

Chemical modulation of autophagy as an adjunct to chemotherapy in childhood and adolescent brain tumors


The cover for issue 81 of Oncotarget features Figure 1, "Molecular Mechanisms of Autophagy," by Servante, et al.

On one face, especially in the early phases of cancer formation, autophagy can act as a cellular housekeeper to eliminate damaged organelles and recycle macromolecules, thus acting as tumor suppressor. The researchers present an overview of the relevance of autophagy in central nervous system tumors including how its chemical modulation can serve as a useful adjunct to... continue reading >>

Inherited DNA-repair gene mutations in African American men with prostate cancer


Oncotarget Volume 11, Issue 4: Pathogenic or likely pathogenic alterations in these 14 DNA repair genes were less likely to be detected in African Americans as compared to Caucasians.

Upon a more in-depth analysis, the risk of germline pathogenic/likely pathogenic BRCA mutations was similar between the two populations whereas there was a lower risk among African Americans for the non-BRCA mutations.

Dr. Oliver Sartor from the Tulane Cancer Center at the Tulane University of School of Medicine ... continue reading >>

Characterization of unique PMEPA1 gene splice variants (isoforms d and e) from RNA Seq profiling provides novel insights into the prognostic evaluation of prostate cancer


The cover for issue 4 of Oncotarget features Figure 8, "Model for biological function categorization of PMEPA1 isoforms (c, d, and e) in the context of prostate cancer," by Sharad, et al.

In addition to 4 reported PMEPA1 isoforms, one novel isoform PMEPA1-e was identified with RNA Seq analysis of hormone-responsive VCa P, LNCa P cells and human prostate cancer samples from The Cancer Genome Atlas dataset.

The researchers analyzed the structures, expressions, biological functions and clinical... continue reading >>

Molecular analysis of the dual targeting of the epidermal growth factor receptor and the O6-methylguanine-DNA methyltransferase with a double arm hybrid molecule


The cover for issue 80 of Oncotarget features Figure 5, "Molecular modeling of MR30," by Rupp, et al.

In order to block uncoupled events associated with EGFR and MGMT, the research team designed MR30, a single molecule termed combi-molecule that contains a quinazoline arm targeted to EGFR and an O6-benzylguanine moiety to block MGMT. Molecular analysis of the mechanism of action of its two arms showed that: it could block EGFR phosphorylation, down-regulate the RAF-MAPK and the PI3K-AKT... continue reading >>

Deletion of the glucocorticoid receptor chaperone FKBP51 prevents glucocorticoid-induced skin atrophy


The cover for issue 78 of Oncotarget features Figure 4, "Effect of FKBP51 KO on glucocorticoid response and Akt/mTOR in HaCaT human keratinocytes," by Baida, et al.

Here, the researchers used FKBP51 knockout mice to determine FKBP51s role in the major adverse effect of topical glucocorticoids, skin atrophy. Furthermore, despite the absence of inhibitory FKBP51, the basal level of expression and glucocorticoid activation of GR target genes were not increased in FKBP51 KO skin or... continue reading >>

In preclinical study, the phenanthrene derivative PJ34 exclusively eradicates human pancreatic cancer cells in xenografts


Prof. Malka Cohen-Armon and her team at Tel Aviv University's Sackler Faculty of Medicine choose Oncotarget for a third time amongst leading medical journals like The New England Journal of Medicine, Nature or The Lancet to publish groundbreaking preclinical cancer research.

Here's more: Recent reports demonstrate an exclusive eradication of a variety of human cancer cells by the modified phenanthridine PJ34. The efficient eradication of malignant cells in human pancreatic cancer xenografts... continue reading >>

Oncotarget | The virome of HPV-positive tonsil squamous cell carcinoma and neck metastasis


Oncotarget Volume 11, Issue 3 features Figure 3, "Hierarchical clustering of tonsil squamous cell carcinoma cohorts based on viral signature detection pattern with associated pathological features (perineural invasion (PNI), lymphovascular invasion (LVI), and tumor stage (T stage))," by Carey, et al.

In this prospective study, a pan-pathogen microarray was used to determine the virome of early stage, p16-positive OPSCC and neck metastasis treated with transoral robotic surgery and neck... continue reading >>

RN765C, a low affinity EGFR antibody drug conjugate with potent anti-tumor activity in preclinical solid tumor models


The cover for issue 71 of Oncotarget features Figure 1B, "Schematic representation to illustrate the differential binding and internalization of low affinity EGFR-ADC on normal cells versus tumor cells that express higher level of the receptors," by Wong, et al.

Potent in vitro cytotoxicity of RN765C, with nanomolar to subnanomolar EC50, was observed on a panel of cancer cell lines expressing moderate to high level of EGFR. Mechanistically, RN765C has multiple modes of action: inducing payload ... continue reading >>

Outcome analysis of Phase I trial patients with metastatic KRAS and/or TP53 mutant non-small cell lung cancer


The cover for issue 70 of Oncotarget features Figure 4B, "BRAF/MEK inhibitor-based phase 1 trial therapy according to BRAF or KRAS hotspot mutation status," by Wang, et al.

About 10%, 18%, 36%, and 36% of the patients had metastatic KRAS+/TP53+, KRAS+/TP53-,KRAS-/TP53+, and KRAS-/TP53- NSCLC, respectively. Introduction of the evolutionary action score system of TP53 missense mutations enabled the research team to identify a subgroup of NSCLC patients with low-risk mutant p53 proteins having a ... continue reading >>

mTORC1/2 inhibition re-sensitizes platinum-resistant ovarian cancer by disrupting selective translation of DNA damage and survival mRNAs


The cover for issue 69 of Oncotarget features Figure 5, "qRT-PCR analysis of select mRNAs in mTORC1/2 inhibited cells with and without carboplatin treatment," by David-West, et al.

Using platinum-resistant OVCAR-3 cells treated with the selective mTORC1/2 inhibitor INK128/MLN128, the research team conducted genome-wide transcription and translation studies and analyzed the effect on cell proliferation, AKT-mTOR signaling and cell survival, to determine whether carboplatin resistance involves... continue reading >>

Bladder cancer detection by urinary extracellular vesicle mRNA analysis


The cover for issue 67 of Oncotarget features Figure 4, "ROC curve analysis of urinary EV mRNA markers in various stages of bladder cancer," by Murakami, et al.

Biomarker candidates were identified through RNA-seq analysis of urinary EV from patients with non-muscle invasive bladder cancer, advanced urothelial cancer, no residual tumor after TURBT, and healthy and disease controls. These genes allowed detection of non-muscle invasive bladder cancer as well as pT2 and higher muscle invasive... continue reading >>

Tumor cell density regulates matrix metalloproteinases for enhanced migration


The cover for issue 66 of Oncotarget features Figure 4, "RNA sequencing of PDX tumors," by Jayatilaka, et al.

Cancer cell density changes dramatically during the early growth of a primary tumor and during the early seeding steps of secondary tumors and has been implicated in playing an important role in regulating metastasis and drug resistance. Local tumor cell density also plays a role in the responsiveness of cells to matrix metalloproteinases inhibitors, such as Batimastat, Marimastat,... continue reading >>

The targeted LHRH analog AEZS-108 alters expression of genes related to angiogenesis and development of metastasis in uveal melanoma


The cover for issue 2 of Oncotarget features Figure 5, "MASPIN can prevent the formation of UPA - UPA-receptor complex by a single step, and thus decrease the possibility of the abnormal degradation of the ECM, the development metastasis and angiogenesis," by Fodor, et al.

In the present study, the research team investigated AEZS-108 induced cytotoxicity and the altered mRNA expression profile of regulatory factors related to angiogenesis and metastasis in LHRH receptor-positive OCM3 cells.

Th... continue reading >>

Genomic mutations and histopathologic biomarkers in Y90 radioembolization for chemorefractory colorectal liver metastases


The cover for issue 65 of Oncotarget features Figure 5, "Waterfall plot showing response by % change in tumor size after Y-90 radioembolization," by Dendy, et al.

To investigate mutational load and histologic biomarkers as prognostic factors in patients with chemorefractory colorectal liver metastases treated with Y-90 radioembolization therapy. Single institution retrospective study of patients with CRLM who received Y-90 radioembolization after undergoing molecular testing was performed.... continue reading >>

RNA based individualized drug selection in breast cancer patients without patient-matched normal tissue


The cover for issue 64 of Oncotarget features Figure 2, "Principal component analysis based on gene expression," by Forster, et al.

While standard RNA expression tests stratify patients into risk groups, RNA-Seq can guide personalized drug selection based on expressed mutations, fusion genes, and differential expression between tumor and normal tissue. This research identified breast cancer related and drug related genes that are expressed uniformly across our normal samples.

Normal... continue reading >>

PD1 is expressed on exhausted T cells as well as virus specific memory CD8+ T cells in the bone marrow of myeloma patients


The cover for issue 62 of Oncotarget features Figure 3, "High tumor load is associated with increased number of CD8+EOMEShigh T betlow cells," by Sponaas, et al.

Here, the researchers found similar proportions of PD1+ CD8+ T cells and similar levels of PD1 expression on CD8+ T cells in the bone marrow of myeloma patients and healthy controls. PD1 expression on CD8+ T cells did not correlate with tumor load suggesting that at least some of the PD1+ CD8+ T cells were specific for non-myeloma... continue reading >>

Palbociclib resistance confers dependence on an FGFR-MAP kinase-mTOR-driven pathway in KRAS-mutant non-small cell lung cancer


The cover for issue 60 of Oncotarget features Figure 8, "Modeling of palbociclib resistance in KRAS-mutant NSCLC cells and effects of MAP kinase pathway inhibition," by Haines, et al.

The research demonstrates that KRAS-mutant NSCLC cell lines are initially sensitive to the CDK4/6 inhibitor palbociclib, but readily acquire resistance associated with increased expression of CDK6, D-type cyclins and cyclin E. Resistant cells also demonstrated increased ERK1/2 activity and sensitivity to MEK and... continue reading >>

Identification of signature genes associated with therapeutic resistance to anti-VEGF therapy


The cover for issue 1 of Oncotarget features Figure 5, "APLN overexpression correlates with worsened prognosis in ovarian cancer patients treated with bevacizumab," by Jaiprasart, et al.

To establish a molecular signature of this resistance in ovarian cancer, the authors developed preclinical tumor models of adaptive resistance to chronic anti-VEGF treatment.

These findings link signature gene expressions with anti-VEGF response, and may thus provide novel targetable mechanisms of clinical... continue reading >>

High AGR2 protein is a feature of low-grade endometrial cancer cells


The cover for issue 59 of Oncotarget features Figure 4, "The expression of AGR2 in metastatic lesions," by Kamal, et al.

Elevated AGR2 protein expression-scores were associated with a high expression of estrogen alpha, progesterone, androgen receptors and early clinical stages. High-AGR2 protein levels were associated with better overall survival in all ECs, but in highly-ER -expressing ECs, AGR2 associated with unfavorable patient outcome. The association between high AGR2 and progressive... continue reading >>

Chromatin-associated APC regulates gene expression in collaboration with canonical WNT signaling and AP-1


The cover for issue 58 of Oncotarget features Figure 7, "Models of WNT-mediated transcriptional activation and repression involving TCF7L2, AP-1, β-catenin and APC," by Hankey, et al.

The APC protein performs multiple tumor suppressor functions including negative regulation of the canonical WNT signaling pathway by both cytoplasmic and nuclear mechanisms. Published reports that APC interacts with -catenin in the chromatin fraction to repress WNT-activated targets have raised the possibility... continue reading >>

Identifying the druggable interactome of EWS-FLI1 reveals MCL-1 dependent differential sensitivities of Ewing sarcoma cells to apoptosis inducers


The cover for issue 57 of Oncotarget features Figure 1A, "Schematic representation of our systematic approach developed to identify effective compounds and biological vulnerabilities in EwS.," by Tsafou, et al.

The research group identified differential sensitivities of Ewing sarcoma cells to BCL-2 family inhibitors dependent on the EWS-FLI1 regulome including altered MCL-1 expression and subcellular localization. This study facilitates the selection of effective targeted approaches for future ... continue reading >>

Low-dose metronomic cyclophosphamide complements the actions of an intratumoral C-class CpG TLR9 agonist to potentiate innate immunity and drive potent T cell-mediated anti-tumor responses


The cover for issue 68 of Oncotarget features Figure 4, "Gene expression changes to the TME demonstrate sequential development of innate and adaptive immune responses," by Leong, et al.

Intratumoral injection of SD-101 induces significant anti-tumor immunity in preclinical and clinical studies, especially when combined with PD-1 blockade.

Combination therapy generated CD8+ T cell dependent immunity leading to rejection of both non-injected and injected tumors and long-term survival, even in... continue reading >>

Anetumab ravtansine inhibits tumor growth and shows additive effect in combination with targeted agents and chemotherapy in mesothelin-expressing human ovarian cancer models


The cover for issue 75 of Oncotarget features Figure 7, "Antitumor efficacy of anetumab ravtansine in combination with bevacizumab in human ovarian cancer xenograft models in mice," by Quanz, et al.

Herein, the research team investigated the antitumor efficacy of the mesothelin-targeting antibody-drug conjugate anetumab ravtansine as a novel treatment option for ovarian cancer in monotherapy and in combination with the antitumor agents pegylated liposomal doxorubicin, carboplatin, copanlisib... continue reading >>

Leukaemia inhibitory factor is associated with treatment resistance in oesophageal adenocarcinoma


The cover for issue 72 of Oncotarget features Figure 5A, "Elevated levels of secreted LIF negatively correlates with lymphocyte infiltration in human OAC pre-treatment biopsies," by Buckley, et al.

Inflammation influences OAC given the increased risk of cancer development and poor outcome for obese patients where altered secretion of adipokines and cytokines from adipose tissue contributes a pro-tumourigenic environment. Furthermore, significantly higher circulating levels of LIF were present ... continue reading >>

Nuclear up regulation of the BRCA1-associated ubiquitinase BAP1 is associated with tumor aggressiveness in prostate cancers lacking the TMPRSS2:ERG fusion


The cover for issue 67 of Oncotarget features Figure 1, "Examples of (A) negative, (B) weak, (C) moderate and (D) strong BAP1 staining in prostate cancer and (E) BAP1 staining of cancerous (Ea) and normal (Eb) prostate glands in the same TMA spot," by Steurer, et al.

Studies on the expression and prognostic role of BAP1 in prostate cancer are currently lacking.

The research team used a tissue microarray of 17,747 individual prostate cancer samples linked with comprehensive pathological,... continue reading >>

Can computer-aided diagnosis assist in the identification of prostate cancer on prostate MRI? a multi-center, multi-reader investigation


The cover for issue 73 of Oncotarget features Figure 2, "Benefit of CAD in TZ tumor identification," by Gaur, et al.

For prostate cancer detection on prostate multiparametric MRI, the Prostate Imaging-Reporting and Data System version 2 and computer-aided diagnosis systems aim to widely improve standardization across radiologists and centers.

Dr. Baris Turkbey from the Molecular Imaging Program, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA said "Men with... continue reading >>

Delayed adverse events in phase I trials of molecularly targeted and cytotoxic agents


The cover for issue 74 of Oncotarget features Figure 4, "Treatment interruptions and dose modifications," by Jordan, et al.

Mean AE totals for CCs or MTAs respectively was 4.7 versus 3.0 in cycle 1, 3.8 versus 2.8 in cycles 2-6.Patients on CCs had higher mean AEs in six cycles compared to those on MTAs. For MTAs, more frequent incidence of first grade 3/4 AEs after cycle 1 supports incorporation of delayed AEs into recommendations for Phase 2 dosing.

Dr. Debashis Sarker from the School of... continue reading >>

3'Igh enhancers hs3b/hs4 are dispensable for Myc deregulation in mouse plasmacytomas with T(12;15) translocations


The cover for issue 77 of Oncotarget features Figure 2, "In mouse PCTs, deletion of hs3b-4 does not affect the pattern of chromosomal translocations but significantly increases targeting of Sμ for T(12;15)," by Kovalchuk, et al.

To elucidate the role of the Igh3RR in tumorigenesis, we induced PCTs in Bcl-xL-transgenic mice deficient for the major Igh3RR enhancer elements, hs3b and hs4. Cre-mediated deletion of the Igh3RR resulted in gradual reduction of Myc expression, loss of proliferative... continue reading >>

A small molecule regulator of tissue transglutaminase conformation inhibits the malignant phenotype of cancer cells


The cover for issue 76 of Oncotarget features Figure 2, "The identification of TTGM 5826 as a potential modulator of tTG conformation," by Katt, et al.

This raises the possibility that strategies directed toward causing tTG to maintain an open state could potentially provide a therapeutic benefit for cancers in which tTG is highly expressed. Thus, TTGM 5826 represents the lead compound for a new class of small molecules that promote the toxicity of cancer cells by stabilizing the open state of ... continue reading >>

Single cell correlation analysis of liquid and solid biopsies in metastatic colorectal cancer


The cover for issue 66 of Oncotarget features Figure 1, "HD-SCA sample processing and CRC analysis overview," by Gerdtsson, et al.

The research team has established an approach for measuring patient-specific circulating and solid cell concordance by introducing tumor touch preparations to the High-Definition Single Cell Analysis workflow for high-resolution cytomorphometric characterization of metastatic colorectal cancer.

Combined with the association of circulating cells with tumor burden... continue reading >>

Loss of KIBRA function activates EGFR signaling by inducing AREG


The cover for issue 52 of Oncotarget features Figure 5, "Low KIBRA expression predicts poor breast cancer patient outcome," by Mussell, et al.

The clinical significance of KIBRA deregulation and the underlying mechanisms by which KIBRA regulates breast cancer initiation and progression remain poorly understood. Mechanistically, the researchers observed that inhibiting KIBRA induced growth factor-independent cell proliferation in 2D and 3D culture due to the secretion of amphiregulin, an... continue reading >>

Targeting the invincible barrier for drug delivery in solid cancers: interstitial fluid pressure


The cover for issue 87 of Oncotarget features Figure 1, "The survival rate of genetically engineered mice with pancreatic ductal adenocarcinoma treated with a weekly injection of nano-albumin bound paclitaxel (NAB-paclitaxel) alone (orange line, n = 4), NAB-paclitaxel 3 hours after CYT-6091 treatment (green line, n = 4), and vehicle control (blue line, n = 3)," by Libutti, et al.

Although a number of new systemic therapeutic options in patients with advanced solid cancers have emerged due to... continue reading >>

Molecular profiling of advanced breast cancer tumors is beneficial in assisting clinical treatment plans


This was a retrospective review of a cohort of patients that were profiled using established IHC biomarkers, along with fragment analysis, in situ hybridization and sequencing.

Their treatments were either matched or unmatched based on whether the treatment chosen by their physician was predicted to be beneficial by Caris Life Sciences using the molecular profile of the tumor.

Comparing these two groups showed that the matched treatment group had an increase of 31% in survival compared to the ... continue reading >>

Dynamic changes during the treatment of pancreatic cancer


This detailed analysis of the clinical descriptions, imaging, pathology, molecular and cellular evolution of the tumors, treatments and responses to chemotherapy, targeted therapies and immunotherapies as well as attempts at the development of personalized medical treatments for a single patient should provide a valuable guide to future directions in cancer treatment.

"They all sacrificed time and effort from other research projects and activities, because they all came to appreciate the... continue reading >>

Modulation of proliferation factors in lung adenocarcinoma with an analysis of the transcriptional consequences of genomic EGFR activation


The cover for issue 65 of Oncotarget features Figure 7, "EGFR activated cases compared to pathway markers," by Kucherlapati, et al.

Molecular subtypes based on copy number, DNA methylation, and mRNA expression had variable proliferation levels, the highest correlating with decreased survival.

Significantly, results suggest EGFR over expression and activation are early alterations that likely stall the replication complex through PCNA phosphorylation creating replication stress responsible for ... continue reading >>

Real-time scratch assay reveals mechanisms of early calcium signaling in breast cancer cells in response to wounding


The connections between mechanically-activated ATP signaling, purinergic receptors, calcium signaling, and EMT in vitro cancer biology are mounting, but are still not well-defined.

Dr. Stephen J.P. Pratt and Dr. Stuart S. Martin research team said that "By first experimentally defining rapid mechanically-induced calcium signaling in cancer cells, this work sets a foundation to explore mechano-calcium relationships driving malignant progression"

There is growing evidence supporting the notion... continue reading >>

Clinical significance of the correlation between PLCE 1 and PRKCA in esophageal inflammation and esophageal carcinoma


This study analyzed the expression levels of and correlation between PLCE1 and PRKCA in human esophagitis, carcinogen NMBA-induced rat esophagus, PLCE1 genetic deficient mouse esophageal epithelial tissues and human esophageal cancer cell line, integrated with Online oncology data sets.

The research team found that the expression levels of both PLCE1 and PRKCA were significantly elevated in human esophagitis, esophageal squamous cell carcinoma, Barretts esophagus, esophageal adenocarcinoma and ... continue reading >>

NK cell expression of natural cytotoxicity receptors may determine relapse risk in older AML patients undergoing immunotherapy for remission maintenance


In younger (<60 years old, n = 37) and older patients (>60 years old, n = 47), treatment with HDC/IL-2 resulted in an expansion of CD56bright and CD16+ NK cells in blood along with an increased NK cell expression of the natural cytotoxicity receptors NKp30 and NKp46.

Dr. Anna Martner from the TIMM Laboratory, Sahlgrenska Cancer Center at the University of Gothenburg in Gothenburg, Sweden said, "At diagnosis, approximately 70% of patients with acute myeloid leukemia (AML) are >60 years old.... continue reading >>

Preliminary observations on soluble programmed cell death protein-1 as a prognostic and predictive biomarker in patients with metastatic melanoma treated with patient-specific autologous vaccines


Blood samples obtained during a randomized trial in patients with metastatic melanoma were tested from 22 patients treated with a tumor cell vaccine and 17 treated with a dendritic cell vaccine.

Among DCV-treated patients, these sPD-1 criteria appropriately classified 8/10 of 3-year survivors, and 6/7 of patients who did not survive three years.

Dr. Robert O. Dillman from AIVITA Biomedical, Inc. in Irvine, CA, USA said, "PD-1 (CD279) was first described by Tasuku Honjo and colleagues at Kyoto ... continue reading >>

A mouse model of prostate cancer bone metastasis in a syngeneic immunocompetent host


The cover for issue 64 of Oncotarget features Figure 5, "In vivo and ex-vivo growth kinetics of B6CaP," by Simons, et al.

The Research Team reports the establishment of B6Ca P, an allograft tumor line from a Hi-Myc transgenic mouse that had been backcrossed onto C57BL/6J background.

This is the first example of a prostate-derived tumor line that shows frequent metastasis to bone and grows in an immunocompetent host, making this model useful for studying mechanisms of bone metastasis and tumor ... continue reading >>

Application of C. elegans cancer screening test for the detection of pancreatic tumor in genetically engineered mice


Previously, the research group developed a novel method to detect various kinds of human cancer using nematode Caenorhabditis elegans that respond to cancer odor in urine; however, whether this method is useful for non-human species remains to be understood.

The chemotactic analysis indicated that C. elegans avoids urine of healthy recipient mice, while they tended to be attracted to urine of mice with Kras G12D. The research team's study demonstrated that C. elegans can recognize the odor of... continue reading >>

PTEN deletion drives acute myeloid leukemia resistance to MEK inhibitors


To identify possible causes of resistance to MEK inhibition, this research team generated a model of resistance by long-term treatment of AML cells with AZD6244.

Remarkably, resistance to MEK inhibition was due to acquired PTEN haploinsufficiency, rather than mutation of MEK.

Dr. Andrew S. Moore from the University of Queensland Diamantina Institute and the Child Health Research Centre at the University of Queensland in Woolloongabba, Australia as well as the Oncology Services Group at... continue reading >>

CLCA4 inhibits bladder cancer cell proliferation, migration, and invasion by suppressing the PI3K/AKT pathway


Overexpression of CLCA4 profoundly attenuated the proliferation, growth, migratory and invasive capabilities of bladder cancer cells, whereas CLCA4 knockdown had the opposite effect.

This study suggests that CLCA4 may represent a promising prognostic biomarker for bladder cancer and provides a possible mechanism for bladder cancer growth and invasion.

Dr. Zhaohui Chen from the Department of Urology, Union Hospital, Tongji Medical College at the Huazhong University of Science and Technology in ... continue reading >>

NOTCH1 signaling in oral squamous cell carcinoma via a TEL2/SERPINE1 axis


The cover for issue 63 of Oncotarget features Figure 6, "Inverse relationship between ETV7 and SERPINE1 in OSCC," by Salameti, et al.

In this study, the research team investigated NOTCH1 mutations in keratinocyte lines derived from OSCC biopsies that had been subjected to whole exome sequencing.

One line, SJG6, was found to have truncating mutations in both NOTCH1 alleles, resulting in loss of NOTCH1 expression.

Overexpression of the NOTCH1 intracellular domain in SJG6 cells promoted cell... continue reading >>

Mutation of the co-chaperone Tsc1 in bladder cancer diminishes Hsp90 acetylation and reduces drug sensitivity and selectivity


The researchers have recently identified the tumor suppressor tuberous sclerosis complex 1 as a new co-chaperone of Hsp90 that affects Hsp90 binding to its inhibitors.

Their findings suggest that TSC1 status may predict response to Hsp90 inhibitors in patients with bladder cancer, and co-targeting HDACs can sensitize tumors with Tsc1 mutations to Hsp90 inhibitors.

Dr. Mehdi Mollapour and Dr. Dimitra Bourboulia said, "Over 80,000 people will be diagnosed with bladder cancer and approximately... continue reading >>

Cell-free DNA in newly diagnosed patients with glioblastoma – a clinical prospective feasibility study


The aim was to test the feasibility of using cell-free DNA to support evaluation of treatment response, pseudo-progression and whether progression could be found before clinical and/or radiologic progression.

Cf DNA fluctuated during treatment with the highest levels before diagnostic surgery and at progression.

An increase was seen in 3 out of 4 patients at the time of progression while no increase was seen in 3 out of 4 patients without progression.

Dr. Dorte Schou Nørøxe from the... continue reading >>

Elucidating drivers of oral epithelial dysplasia formation and malignant transformation to cancer using RNAseq


To identify markers of early disease, the research team performed RNA sequencing of 19 matched HPV negative patient trios: normal oral mucosa, dysplasia and associated OSCC.

They highlight novel coding and non-coding candidates for involvement in oral dysplasia development and malignant transformation, and speculate on how their findings may guide further translational research into the treatment of oral dysplasia.

Dr. Lucy F. Stead from Precancer Genomics at Leeds Institute of Cancer and... continue reading >>

The discovery of potent ribosomal S6 kinase inhibitors by high-throughput screening and structure-guided drug design


The research shows that the resulting oxadiazole-substituted aza-benzimidazole is a potent and ligand efficient S6 kinase inhibitor, which blocks the phosphorylation of RPS6 at Ser235/236 in TSC negative HCV29 human bladder cancer cells by inhibiting S6 kinase activity and thus provides a useful tool compound to investigate the function of S6 kinases.

Dr. Rob L.M. van Montfort and Dr. Keith Jones said "The 70 KDa ribosomal S6 kinases (S6K) RPS6KB1 (S6K1) and RPS6KB2 (S6K2) are key effectors of ... continue reading >>

Tumor vessel normalization after aerobic exercise enhances chemotherapeutic efficacy


Targeted therapies aimed at tumor vasculature are utilized in combination with chemotherapy to improve drug delivery and efficacy after tumor vascular normalization.

The research team's data in mouse models indicate that activation of calcineurin-NFAT-TSP1 signaling in endothelial cells plays a critical role in exercise-induced shear stress mediated tumor vessel remodeling.

They show that moderate aerobic exercise with chemotherapy caused a significantly greater decrease in tumor growth than... continue reading >>

Avoidance of apoptotic death via a hyperploid salvage survival pathway after platinum treatment in high grade serous carcinoma cell line models


The cover for issue 62 of Oncotarget features Figure 7, "Proposed model of the hyperploid pathway as a salvage survival strategy regulated by the G2-M checkpoint," by Yeung, et al.

Subpopulations of tumor cells may exhibit diverging behaviors from the bulk tumor due to an alternate stress response that diverts tumor cells from apoptotic death.

In this study, the researcher identified a salvage survival pathway in which G2-arrested tumor cells bypassed apoptosis and progressed through aberrant ... continue reading >>

Consuming cholera toxin counteracts age-associated obesity


Here the research team tested a safe and well-established microbe-based immune adjuvant to restore immune homeostasis and counteract inflammation-associated obesity in animal models.

Taken together, they concluded that oral vaccination with cholera toxin B helps stimulate health-protective immune responses that counteract age-associated obesity.

Dr. Susan E. Erdman from the Division of Comparative Medicine, at the Massachusetts Institute of Technology in Cambridge, MA, United States said, "The... continue reading >>

Therapeutic inhibition of Mcl-1 blocks cell survival in estrogen receptor-positive breast cancers


While estrogen receptor - + breast cancers express high levels of three anti-apoptotic Bcl-2 family members, pharmacological inhibition of Bcl-2 and/or Bcl-xL fails to induce cell death in ER + breast cancer cell lines, due to rapid and robust Mcl-1 upregulation.

Cells treated with a pharmacological inhibitor of cap-dependent translation, or with the mTORC1 inhibitor RAD001/everolimus, displayed reduced protein levels of Mcl-1 under basal conditions, and failed to upregulate Mcl-1 protein... continue reading >>

Liquid biopsy monitoring uncovers acquired RAS-mediated resistance to cetuximab in a substantial proportion of patients with head and neck squamous cell carcinoma


46% of patients with on-treatment disease progression showed acquired RAS mutations, while no RAS mutations were found in the non-progressive subset of patients, indicating that acquisition of RAS mutant clones correlated significantly with clinical resistance.

RAS mutations account for acquired resistance to EGFR-targeting in a substantial proportion of HNSCC patients, even though these tumors are rarely mutated at baseline.

Dr. Mascha Binder from the Department of Oncology and Hematology... continue reading >>

Molecular mechanisms of human IRE1 activation through dimerization and ligand binding


IRE1 autophosphorylation is coupled to RNase activity through formation of a back-to-back dimer, although the conservation of the underlying molecular mechanism is not clear from existing structures.

The researchers have developed a compound that potently inhibits human IRE1 kinase activity while stimulating XBP1 splicing.

A crystal structure of the inhibitor bound to IRE1 shows an increased ordering of the kinase activation loop.

Dr. Richard Bayliss and Dr. Ian Collins said "The endoplasmic ... continue reading >>

Microsatellite stability and mismatch repair proficiency in nasopharyngeal carcinoma may not predict programmed death-1 blockade resistance


PET-CT scan revealed a space-occupying lesion in the left lung, and the pathologic result confirmed the occupying lesion originated from NPC. Meanwhile, both immunohistochemistry and PCR revealed that the occupying lesion belonged to pMMR NPC. We provide the first report that pembrolizumab has a confirmed objective response to microsatellite stability and pMMR NPC, and two biomarkers may not be sufficient to identify patients who might be resistant to such treatment in NPC.

Dr. Qin Lin from... continue reading >>

High expression of apoptosis protein (Api-5) in chemoresistant triple-negative breast cancers: an innovative target


The cover for issue 61 of Oncotarget features Figure 4, "The influence of stress conditions on API-5 expression and inhibition," by Bousquet, et al.

78 TNBC biopsies from patients with different responses to chemotherapy were analysed for API-5 expression before any treatment.

Further studies on API-5 expression and inhibition were performed on patient-derived TNBC xenografts, one highly sensitive to chemotherapies and the other resistant to most tested drugs.

Clinical analyses of the 78... continue reading >>

Clinical benefit of a precision medicine based approach for guiding treatment of refractory cancers


19 of 44 patients treated with genomically guided therapy attained a PFS ratio 1.3 vs. 3 of 57 treated with non-genomically guided therapy.

Similarly, overall PFS ratios were higher for patients with genomically guided therapy vs non-genomically guided therapy.

Patients with refractory metastatic cancer who receive genomically guided therapy have improved PFS ratios and longer median PFS compared to patients who do not receive genomically guided therapy.

Dr. Bryan P. Schneider from the... continue reading >>

Secretome of pleural effusions associated with non-small cell lung cancer (NSCLC) and malignant mesothelioma: therapeutic implications


The cover for issue 60 of Oncotarget features Figure 3, "Comparison of cytokine levels grouped by function," by Donnenberg, et al.

Cryopreserved cell-free PE fluid from 101 NSCLC patients, 8 mesothelioma and 13 with benign PE was assayed for a panel of 40 cytokines/chemokines using the Luminex system.

Comparing NSCLC PE and published plasma levels of CAR-T recipients, both were dominated by sIL-6R and IL-6 but NSCLC PE had more VEGF, FGF2 and TNF, and less IL-2, IL-4, IL-13, IL-15, MIP1 and... continue reading >>

Dynamic transition of the blood-brain barrier in the development of non-small cell lung cancer brain metastases


The cover for issue 59 of Oncotarget features Figure 9, "A schematic representation of the blood-brain barrier (BBB), brain around tumor region (BAT) and blood-tumor barrier (BTB) in late stage NSCLC brain metastases in an experimental model," by Uzunalli, et al.

Effective drug delivery through the BTB is one of the greatest therapeutic obstacles in treating brain metastases.

Using an experimental model, the researchers defined key changes within the BTB and the BBB in the brain around the... continue reading >>

Kallikrein 6 protease advances colon tumorigenesis via induction of the high mobility group A2 protein


The cover for issue 58 of Oncotarget features Figure 5, "Representative images of KLK6 and HMGA2 IHC staining in the surgical material of a colon cancer patient," by Chen, et al.

In the CRC patients, KLK6 protein levels were elevated in the non-cancerous distant and adjacent tissues, compared to their paired tumor tissues.

Patients with mutant K-RAS tumors had significantly higher level of KLK6 protein in the luminal surface of non-cancerous distant tissue, compared to the corresponding... continue reading >>

Assessment of circularized E7 RNA, GLUT1, and PD-L1 in anal squamous cell carcinoma


The cover for issue 57 of Oncotarget features Figure 2, "Overall survival analysis of GLUT1, PD-L1, and histologic architecture," by Chamseddin, et al.

High levels of circ E7 by quantitative RT-PCR predicted improved overall survival in ASCC and analysis of The Cancer Genome Atlas sequencing from HPV-positive head and neck cancer and cervical cancer suggested high circ E7 marked improved survival in 875 subjects.

While the research team's study suggests that circ E7 levels correlate with... continue reading >>

Encyclopedic tumor analysis for guiding treatment of advanced, broadly refractory cancers: results from the RESILIENT trial


RESILIENT was a single arm, open label, phase II/III study to test if label agnostic therapy regimens guided by Encyclopedic Tumor Analysis can offer meaningful clinical benefit for patients with relapsed refractory metastatic malignancies.

Patients with advanced refractory solid organ malignancies where disease had progressed following 2 lines of systemic treatments were enrolled in the trial.

At study completion, Disease Control was observed in 114 out of 126 patients evaluable per protocol ... continue reading >>

Repurposed quinacrine synergizes with cisplatin, reducing the effective dose required for treatment of head and neck squamous cell carcinoma


The authors have developed the Accelera TED platform to repurpose drugs for HNSCC treatment; using in vitro assays and in vivo models.

Screening a library of clinically-approved drugs identified the anti-malarial agent quinacrine as a candidate, which significantly reduced viability in a concentration dependent manner in five HNSCC cell lines and in six primary HNSCC samples.

In vivo, daily treatment with 100 mg/kg oral quinacrine plus cisplatin significantly inhibited tumor outgrowth,... continue reading >>

Detection of tyrosine kinase inhibitors-induced COX-2 expression in bladder cancer by fluorocoxib A


Cyclooxygenase-2 is overexpressed in bladder cancer cells, making it an attractive molecular target for the detection and treatment of cancer.

The effects of TKIs on bladder cancer in vivo were evaluated using the COX-2-expressing K9TCC 5Lilly xenograft mouse model and detected by fluorocoxib A. The increased COX-2 expression was detected by all tested TKIs in at least one of the tested COX-2-expressing bladder cancer cell lines in vitro.

Dr. Maria Cekanova from the Department of Small Animal ... continue reading >>

Development and analytical validation of a next-generation sequencing based microsatellite instability (MSI) assay


The assay has a clinically relevant five-day turnaround time and can be conducted on as little as 20 ng genomic DNA with a batch size of up to forty samples in a single run.

Assay performance with respect to accuracy, reproducibility, precision as well as control sample performance was estimated across a wide range of FFPE samples of multiple histologies to address pre-analytical variability, and analytical variability.

Dr. Sean T. Glenn from OmniSeq Inc., Buffalo, NY 14203, USA, the Center... continue reading >>

Safety evaluation of conditionally immortalized cells for renal replacement therapy


Here, the research team assessed the safety of conditionally immortalized proximal tubule epithelial cells for bioartificial kidney application, by using in vitro assays and athymic nude rats.

They demonstrate that these cells do not possess key properties of oncogenically transformed cells, including anchorage-independent growth, lack of contact inhibition and apoptosis-resistance.

Taken together, this study lays an important foundation towards bioartificial kidney development by confirming... continue reading >>

New insights into the genomic landscape of meningiomas identified FGFR3 in a subset of patients with favorable prognoses


The identification of oncogenic mutations has provided further insights into the tumorigenesis of meningioma and the possibility of targeted therapy.

Interestingly, the authors identified a number of mutations in non-NF2 genes, including a hotspot TERTp c.

124: G > A mutation that may be related to poor prognosis and FGFR3 mutations that may represent biomarkers of a favorable prognosis as reported in other cancers.

These mutations can enhance diagnostic accuracy and clinical decision-making.... continue reading >>

Impact of exosomal HIV-1 Tat expression on the human cellular proteome


The cover for issue 54 of Oncotarget features Figure 2, "Comparative proteomic profiling of the peptides/proteins identified from 293T, IL16lamp2b and mExo-Tat samples," by Lu, et al.

The HIV-1 Tat protein is a potent activator of viral transcription.

The researcher's previous work has demonstrated that exosomal formulations of Tat can reverse HIV-1 latency in primary CD4+ T lymphocytes isolated from long term antiretroviral treated individuals suggesting a potential role for Tat as a... continue reading >>

Inhibition of histone deacetylase 2 reduces MDM2 expression and reduces tumor growth in dedifferentiated liposarcoma


The cover for issue 55 of Oncotarget features Figure 3, "Romidepsin exhibits anti-tumor effect in xenograft model of DDLPS," by Seligson, et al.

Here the researchers present in silico, in vitro, and mouse xenograft studies that suggest that specifically targeting HDAC2 reduces MDM2 expression and has anti-tumor affects in DDLPS. In a murine DDLPS xenograft model, romidepsin reduced tumor growth and lowered tumor MDM2 expression.

Taken together, their data supports the hypothesis that... continue reading >>

One-bead one-compound combinatorial library derived targeting ligands for detection and treatment of oral squamous cancer


The cover for issue 52 of Oncotarget features Figure 6, "Confocal images of LLY13 peptide-dye conjugates taken up by live cells in culture," by Yang, et al.

By screening combinatorial one-bead one-compound peptide libraries against oral squamous cancer cell lines, two cyclic peptide ligands, LLY12 and LLY13 were previously identified.

In vivo and ex vivo near infra-red fluorescence imaging studies confirmed the in vivo targeting efficiency and specificity of LLY13 in oral cancer orthotopic... continue reading >>

Anti-VEGFR2 therapy delays growth of preclinical pediatric tumor models and enhances anti-tumor activity of chemotherapy


The cover for issue 53 of Oncotarget features Figure 5, "Preclinical models of Ewing's sarcoma and osteosarcoma respond to DC101 alone and in combination with cytotoxic chemotherapy," by Lowery, et al.

Several pediatric cancer mouse models responded to single agent DC101-mediated VEGFR2 inhibition with tumor growth delay.

The author's data indicate differential efficacy of targeting the VEGFR2 pathway in pediatric models and support the continued evaluation of VEGFR2 inhibition in combination ... continue reading >>

The phosphorylation status of PIP5K1C at serine 448 can be predictive for invasive ductal carcinoma of the breast


The cover for issue 91 of Oncotarget features Figure 6, "PKD1 expression status and phosphorylation of PIP5K1C at S448 correlate in patient samples of TNBC," by Durand, et al.

By comparing normal breast tissue to carcinoma in situ and invasive ductal carcinoma subtypes, Durand et al. show that the phosphorylation status of PIP5K1C at serine residue 448 can be predictive for breast cancer progression to an aggressive phenotype, while PIP5K1C expression levels are not indicative for... continue reading >>

Oridonin inhibits aberrant AKT activation in breast cancer


The cover for issue 35 of Oncotarget features Figure 3, "Surface plasmon resonance (SPR) analysis of Oridonin binding to AKT1," from Sun, et al.

To date pan-or isoform-selective inhibitor of PI3K inhibitors, AKT inhibitors, mTOR inhibitors, and dual PI3K/mTOR inhibitors have not yielded durable or efficacious clinical results, Oridonin offers promise of both increased efficacy and reduced toxicity compared with single PI3K, AKT, or even dual PI3K/mTOR inhibitors.

Dr. Jean J. Zhao... continue reading >>

Estrogen receptor alpha drives mTORC1 inhibitor-induced feedback activation of PI3K/AKT in ER+ breast cancer


Researchers and authors from the Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA hypothesized that mTORC1 inhibition activates the IGF-1R/Ins R/IRS-1/2 axis in an ER-dependent manner to drive PI3K/AKT and promote cancer cell survival, implicating ER in survival signaling induced by mTORC1 inhibition.

"Approximately 70% of primary breast tumors express estrogen receptor and/or progesterone receptor."

In... continue reading >>

Validating and enabling phosphoglycerate dehydrogenase (PHGDH) as a target for fragment-based drug discovery in PHGDH-amplified breast cancer


The cover for issue 17 of Oncotarget features Figure 4B, "A comparison of the structural elements comprising human PHGDH, sPHGDH and PHGDH-93. Amino acids involved in hydrogen bond formation to the substrate (*) or cofactor NAD+ (*) are highlighted," from Unterlass, et al.

The compounds identified and characterised in this work are structurally different from the reported PHGDH inhibitors CBR-5884 and NCT-503, and thus provide a new starting point for the design of potent and selective... continue reading >>

Targeting autophagy sensitises lung cancer cells to Src family kinase inhibitors


The cover for issue 44 of Oncotarget features Figure 6A, "Autophagy inhibition enables dasatinib to reduce tumour volume in A549 mice xenografts," by Rupniewska, et al.

Taken together, this data suggests that the clinical failure of SRC TKIs in the treatment of NSCLC is due to the induction of intratumoural autophagy by these compounds that prevents apoptosis.

The inhibition of autophagy in combination with classical and targeted chemotherapy is currently the subject of numerous... continue reading >>

Frequently rearranged and overexpressed δ-catenin is responsible for low sensitivity of prostate cancer cells to androgen receptor and β-catenin antagonists


The cover for issue 36 of Oncotarget features Figure 4C, "A cartoon depicts binding complex of catenin proteins and E-cadherin in LNCaP cells, proposed on pull down experiments," from Zhang, et al.

The research shows that δ-catenin in PCa induces β-catenin which, in turn, impacts responses to existing androgen deprivation therapy and currently under development beta-catenin inhibitors.

Dr. Irina V. Kovtun said "Collectively our data suggest that PCa cells with overstimulated δ‐caten... continue reading >>

Selinexor reduces the expression of DNA damage repair proteins and sensitizes cancer cells to DNA damaging agents


The cover for issue 56 of Oncotarget features Figure 1A, "Selinexor reduces the expression of DDR proteins ," by Kashyap, et al.

The goal of this study was to examine the effects of selinexor, an inhibitor of exportin-1 mediated nuclear export, on DNA damage repair and to evaluate the cytotoxic effects of selinexor in combination with DNA damaging agents in cancer cells. In contrast, enhanced cell death was not detected in cells that were pretreated with selinexor then with DDAs. The... continue reading >>

Disulfiram reduces metastatic osteosarcoma tumor burden in an immunocompetent Balb/c or-thotopic mouse model


The cover for issue 53 of Oncotarget features Figure 4, "Image depicting primary (left) and metastatic lung (right) osteosarcoma as visualized by indocyanine green dye angiography," by Crasto, et al.

Disulfiram is an FDA-approved aldehyde dehydrogenase inhibitor that reduces the metastatic phenotype of OS cells in vitro. All treatment groups displayed a significantly reduced quantitative OS metastatic burden compared with controls. Disulfiram treatment resulted in a reduced burden of OS... continue reading >>

Somatic genome alterations in relation to age in lung squamous cell carcinoma


The cover for issue 63 of Oncotarget features Figure 3, "GSEA value of “ECM-Receptor Interaction” pathway in high-SI6/low-SI26 and low-SI6/high-SI26 patient sub-cohorts," by Meucci, et al.

The SNPs mutational profiling showed enrichments of smoking-related signature 4 and defective DNA mismatch repair -related signature 6 in younger patients, while the defective DNA MMR signature 26 was enriched among older patients. We hypothesize that a higher sensitivity to smoking-related damages and ... continue reading >>

Growth hormone-releasing hormone (GHRH) and its agonists inhibit hepatic and tumoral secretion of IGF-1


The cover for issue 47 of Oncotarget features Figure 6, "MR-409 down-regulates IGF-1 expression in cancer cells," by Cui, et al.

It is difficult to envision that GHRH could be involved in the pathophysiologic control of IGF-1 secretion since the circulating levels of hypothalamic GHRH are very low.

Nobel Prize winner Dr. Andrew V. Schally from the Veterans Affairs Medical Center and University of Miami, Miami, FL, USA said "This paper describes our investigations of the effects of GHRH... continue reading >>

A diagnostic autoantibody signature for primary cutaneous melanoma


The cover for issue 55 of Oncotarget features Figure 4, "(A) Regression tree diagram of the best combination of the identified autoantibody biomarkers. (B) Cumulative sensitivity and specificity of the 10 AAb biomarker panel. (C) ROC curve and AUC of the biomarker combination in cohort 1," by Zaenker, et al.

To improve early stage melanoma detection, the development of a highly sensitive diagnostic test is of utmost importance. This melanoma autoantibody signature may prove valuable for... continue reading >>

Super-enhancers: novel target for pancreatic ductal adenocarcinoma


The cover for issue 16 of Oncotarget features Figure 6, "Schematic representation of effects of GZ17-6.02 inhibiting SE following tumorigenesis in PDAC," by Ghosh, et al.

Differential H3K27AC marks were identified at enhancer regions of genes including c-MYC, MED1, OCT-4, NANOG, and SOX2 that can act as super-enhancers (SE), cluster of genes in non-cancerous, cancerous and metastatic PDAC cell lines. GZ17-6.02 affects acetylation of the genes, reduces transcription of major transcription... continue reading >>

Genomic characterization of metastatic ultra-hypermutated interdigitating dendritic cell sarcoma through rapid research autopsy


The cover for issue 3 of Oncotarget features images of a research autopsy to characterize clonal heterogeneity in a rare hypermutated cancer, by Chen, et al.

The research team's analyses revealed ultra-hypermutation, defined as >100 mutations per megabase, in this patients cancer, which was further characterized by the presence of three distinct mutational signatures including UV radiation and APOBEC signatures.

Truncal alterations, defined as being present in all clonal tumor cell... continue reading >>

Anti-psychotic drug could treat aggressive breast cancer


The cover for issue 79 of Oncotarget features Figure 8, "Summary figure of proposed pimozide mechanisms," by Dakir, et al.

Full text | Audio Podcast

A commonly-used anti-psychotic drug could also be effective against triple negative breast cancer, the form of the disease that is most difficult to treat, new research has found. The study, led by the University of Bradford, also showed that the drug, Pimozide, has the potential to treat the most common type of lung cancer.

Anti-psychotic drugs ... continue reading >>

ONC201 kills breast cancer cells in vitro by targeting mitochondria


The cover for issue 26 of Oncotarget features Figure 8, "Proposed mechanism of action of ONC201," from Greer, et al.

TRAIL, a member of the TNF family of ligands, causes caspase–dependent apoptosis through activation of its receptors, death receptor 4 and DR5.

ONC201 was originally identified as a small molecule that inhibits both Akt and ERK, resulting in dephosphorylation of Foxo3a and thereby induces TRAIL transcription.

Recently, two independent groups, Wafik El Deiry at Fox Chase and ... continue reading >>

PD-L1 expression in medulloblastoma: an evaluation by subgroup


The cover for issue 27 of Oncotarget features Figure 5, "MYC overexpression in DAOY (YM21) does not alter PD-L1 expression," from Martin, et al.

This study evaluated the expression of PD‐L1 and markers of immune mediated resistance in human medulloblastoma, the most common malignant pediatric brain tumor.

In cell lines, SHH MB, which are low‐MYC expressing, demonstrated both constitutive and inducible expression of PD‐L1 while those in Group 3/4 that expressed high levels of MYC had only... continue reading >>

Development of a quantitative pharmacodynamic assay for apoptosis in fixed tumor tissue and its application in distinguishing cytotoxic drug-induced DNA double strand breaks from DNA double strand breaks associated with apoptosis


The cover for issue 24 of Oncotarget features Figure 1, "Workflow for enumeration of cleaved caspase-3 bleb–positive [CC3(bleb)+] cells in FFPE canine tumor tissue," from Dull, et al.

Existing microscopy-based methods of detecting apoptosis, such as TUNEL (terminal deoxynucleotidyl transferase dUTP nick-end labeling), have limited quantitative capabilities due to insufficient signal-to-noise ratios. Researchers at the National Cancer Institute and National Cancer Institute-Frederick have... continue reading >>

OncoDNA announces publication of peer-reviewed study in Oncotarget assessing the utility of its unique biomarker analysis and interpretation platform in clinical decision making


The cover for issue 29 of Oncotarget features Figure 2, "Categorisation of samples analysed," from Laes, et al.

  • - OncoDNA treatment recommendation followed in 60% of cases
  • - 93% of treatment decisions were made based on a holistic approach combining next generation sequencing (NGS) and multiple biomarker analysis provided by OncoDNA
  • - 27% of late-stage patients treated with OncoDNA-recommended therapies had overall survival >12 months, compared to a typical average of no more than six months
... continue reading >>

Analysis of the 9p21.3 sequence associated with coronary artery disease reveals a tendency for duplication in a CAD patient


The cover for issue 20 of Oncotarget features Figure 1B, "The diagram showing a general scheme of TAR cloning of a region of interest (in red) from total genomic DNA (in blue) with a linearized TAR vector containing a yeast selectable marker HIS3, centromeric sequence from chromosome 6 (CEN6) and two unique targeting sequences (hook1 and hook2) homologous to 5′ and 3′ ends of the targeted region," from Kouprina, et al.

Before a conclusive link between the SDs and the cardiovascular diseases... continue reading >>

Preclinical characterization of therapeutic antibodies targeted at the carboxy-terminus of Sonic hedgehog


The cover for issue 18 of Oncotarget features Figure 1, "Schematic of experimental procedures for generation of novel anti-Sonic Hedgehog (Shh) candidate therapeutic antibodies directed at the carboxy (C)-terminal," from Tolani, et al.

Even though the Shh pathway is mainly quiescent in adults, the safety of Shh-targeting with therapeutic antibodies was questioned initially because not only does the N-terminus of the Shh protein play an important role in embryonic development, but Shh also... continue reading >>

Precision oncology in advanced cancer patients improves overall survival with lower weekly healthcare costs


The cover for issue 15 of Oncotarget features Figure 3, "Costs per patient among the health system health plan members in the last 3 months of life, by site of care," from Haslem, et al.

The use of advanced molecular diagnostic technologies, such as Next-Generation Sequencing based gene panel testing, to select targeted therapies in advanced cancer patients is known as precision oncology.

In order to evaluate the impact of precision cancer medicine beyond the PFS window and to determine the... continue reading >>

Prognostic role of elevated mir-24-3p in breast cancer and its association with the metastatic process


The cover for issue 16 of Oncotarget features Figure 4A, "Circos plots depicting 316 deferentially expressed genes (FDR < 0.1) out of 745 target genes detected by TargetScan for mir-24-3p (differentially expressed in patients with high mir-24-3p levels vs. low miR-24)," from Khodadadi-Jamayran, et al.

Prognostic role of elevated mir-24-3p in breast cancer and its association with the metastatic process

Despite improvements in local, regional and systemic therapies for breast cancer, 40,610... continue reading >>

Oncotarget to be Indexed in Highly Esteemed Meta Database


Oncotarget to be Indexed in Highly Esteemed Meta Database
Chan Zuckerberg Initiative's Meta Database increases accessibility of scientific data around the world

ORCHARD PARK, N.Y. - February 21, 2018 - This week, Oncotarget announced that its peer-reviewed research publications will be indexed in Meta, a world-renowned database comprised of a plethora scientific literature, alongside our other Impact Journal publications. Meta was acquired by the Chan Zuckerberg Initiative in an effort to... continue reading >>

Oncotarget: Cancer pioneer employs physics to approach cancer in last research article


The cover for issue 14 of Oncotarget features "Symmetry and symmetry breaking in cancer: a foundational approach to the cancer problem," from Frost, et al.

Oncotarget: Cancer pioneer employs physics to approach cancer in last research article.

Distinguished Professor Donald S. Coffey spent more than 50 years at Johns Hopkins and influenced generations of cancer researchers worldwide.

ORCHARD PARK, New York - (FEBRUARY 20, 2018) - In the cover article of Tuesday's issue of
... continue reading >>

Oncotarget awards grants to four biomedical researchers at Frontiers in Cancer Science


ORCHARD PARK, New York - (Dec. 6, 2017) - Oncotarget, the world's largest oncology peer-reviewed research publication, awarded travel grants enabling four biomedical researchers to attend November's Frontiers in Cancer Science 2017 (FCS 2017) conference in Singapore. The travel sponsorship encourages the discussion of cancer discoveries in support of Oncotarget's commitment to maximizing the circulation of scientific research.

"We're dedicated to the wide dissemination of scientific advances... continue reading >>

Oncotarget: Researchers identify a potential molecular trigger for invasiveness in prostate cancer cells


The cover for issue 58 of Oncotarget features Figure 2C, "Representative confocal imaging of PC-3U cells treated with TGFβ for the indicated time periods," from Gudey, et al.

ORCHARD PARK, New York - (Nov. 20, 2017) - A small protein modification can trigger the aggressive migratory and invasive properties of prostate cancer cells, according to new research published on the cover of Oncotarget. The findings give greater insight into how cancers can move from one location in the body to... continue reading >>

Oncotarget: Researchers identify potential therapeutic target in aggressive breast cancer cells


The cover for issue 57 of Oncotarget features Figure 5A, "Ingenuity pathway analysis was performed using microarray data of E2 regulated genes in MDA-MB-231-ERβ cells following 5 days of treatment and revealed suppression of a cell cycle related network," from Reese, et al.

ORCHARD PARK, New York - (November 15, 2017) - An especially aggressive breast cancer cell can respond to hormone therapy if they express a specific protein known as estrogen receptor beta (ERβ), according to new research pu... continue reading >>

New Oncotarget Podcast Launched Today

Podcast will Extend Reach of Oncotarget to Professional Scientists and the Public

FOR IMMEDIATE RELEASE - ORCHARD PARK, New York - (November 8, 2017) - Oncotarget, the world′s largest oncology peer-reviewed research publication, is set to extend its reach with a series of podcasts that will allow scientists to delve deeper into a variety of research contributions found in the journal.

Subscribers to the new podcast series will gain access to the journal′s most important discoveries through full... continue reading >>

Researchers identify novel therapeutic strategy for drug-resistant thyroid cancers


The cover for issue 49 of Oncotarget features Figures 3 and 6, "Combined therapy with vemurafenib and palbociclib induced thyroid tumor cell death in both naïve and resistant clones, overcoming resistance to single-agent treatments," from Antonello, et al.

A video interview with the corresponding author and an audio version of this research article is also available online.

ORCHARD PARK, New York - (October 18, 2017) - Perhaps the only thing more devastating than being diagnosed with cancer... continue reading >>

Individuals in the US diagnosed with cancer are 2.7 times more likely to declare bankruptcy, than individuals without cancer, study finds


The cover for issue 42 of Oncotarget features Figure 3, "Comparable affordability of 8 patented cancer drugs in 7 countries," from Goldstein, et al.

An audio version of this research article is also available online

ORCHARD PARK, New York - (September 27, 2017) - As advancements in cancer therapies have been making headlines in recent years, cancer drug prices have significantly increased. The remaining question is, what are the economic impacts of the differentiations in cost of FDA approved... continue reading >>

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