Differential gene expression and AKT targeting in triple negative breast cancer


The cover for issue 43 of Oncotarget features Figure 6, "Synergistic effect of carboplatin and ipatasertib in a PDX model of TNBC," by Lin, et al.

Early access programmes were established to allow eligible patients with mCRPC access to cabazitaxel before regulatory approval.

The primary objective was to allow access to cabazitaxel before commercial availability for patients with mCRPC whose disease had progressed during or after chemotherapy with docetaxel; the secondary objective was overall safety.

Dr. Yuan Yuan and Dr. Zhen Chen said, "Triple negative breast cancer (TNBC) accounts for 15–20% of all breast cancers and is characterized by poor overall survival upon disease relapse."

Figure 6: Synergistic effect of carboplatin and ipatasertib in a PDX model of TNBC.

Figure 6: Synergistic effect of carboplatin and ipatasertib in a PDX model of TNBC. The dose of ipatasertib was 20 mg/kg for 9 days, followed by 30 mg/kg for 14 days; the dose of carboplatin was 10 mg/kg for two weeks, followed by 20 mg/kg for 1 week (total 3 doses). (A) PDX tumor volume changes over time; (B) Mice maintained their initial weight throughout the treatment; (C) Tumor volume among different groups: vehicle, ipatasertib, carboplatin, and combination ipatasertib plus carboplatin. *P = 0.05, **P = 0.005.

Unlike hormone receptor positive or HER2/neu positive breast cancer , there is no effective targeted therapy for treatment of TNBC with the exception of those with germline BRCA1/2 mutations or programmed death ligand-1 -expressing TNBCs.

In order to develop effective targeted therapy, it is critical to identify targetable genomic or transcriptomic drivers accountable for chemotherapy resistance.

However, this is highly challenging for TNBC because these tumors are very heterogeneous, with at least four molecular sub-types proposed to date based on transcriptomic mRNA expression.

Large-scale genomic databases such as The Cancer Genome Atlas and Molecular Taxonomy of Breast Cancer International Consortium have provided valuable resources for understanding the biology of primary BC tumors.

Analyzing the genomic and transcriptomic changes between paired primary and recurrent TNBC can provide useful insights to improve our understanding of the underlying tumor heterogeneity and tumor evolution with chemotherapy therapy selection pressure, and potentially lead to identification of novel therapeutic targets.

The Yuan/Chen research team concluded, "A phase I/II clinical is planned for further assessment of the clinical activity of this combination."

Full text - https://doi.org/10.18632/oncotarget.27026

Correspondence to - Yuan Yuan - [email protected] and Zhen Chen - [email protected]

Keywords - AKT, differential expression, AKT targeting, TNBC

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