In The News - Press Releases

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... 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... 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... 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... 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... 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... continue reading >>

Oncotarget Editorial Board Members William G Kaelin Jr. and Gregg L Semenza win 2019 Nobel Prize


NEW YORK, October 10, 2019 - The 2019 Nobel Prize in Physiology or Medicine has been awarded jointly to Oncotarget Editorial Board Members William G. Kaelin Jr. and Gregg L. Semenza for their discoveries of "how cells sense and adapt to oxygen availability", said the Nobel Committee. The pair was named... continue reading >>

Mutation of the co-chaperone Tsc1 in bladder cancer diminishes Hsp90 acetylation and reduces drug sensitivity and selectivity


The cover for issue 56 of Oncotarget features Figure 5, "HDAC inhibition synergizes with Hsp90 inhibition to induce apoptosis in bladder cancer.," Woodford, et al.

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... 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... 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... 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... 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... 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... 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... 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... 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... 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... 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... 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... 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... 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... 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... 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 "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... 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... 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... 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 "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... 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... 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... 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... 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... 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... 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... 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
  • - 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... 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... 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... 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... 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... 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... 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... 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 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... 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... 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 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 -... continue reading >>

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