Despite decades of effort to develop effective therapy and to identify promising new drugs, prostate cancer is lethal once it progresses to castration-resistant disease. Studies show mis-regulation of multiple pathways in castration-resistant prostate cancer (CRPC), reflecting the heterogeneity of the tumors and also hinting that targeting androgen receptor (AR) pathway alone might not be suffi...

Abstract Prostate cancer is heterogeneous and patients would benefit from methods that stratify those who are likely to respond systemic therapy. Here, we employ single-cell assays for transposase-accessible chromatin (ATAC) RNA sequencing in models of early treatment response resistance enzalutamide. In doing so, identify pre-existing treatment-persistent cell subpopulations possess regenerati...

The recent manuscript in New England Journal of Medicine by Antonarakis et al. [1] has important clinical implications. This study evaluates mRNA expression of a particular androgen receptor splice variant-7 (AR-V7), in circulating tumor cells (CTCs) from metastatic castrate-resistant prostate cancer (mCRPC) patients receiving enzalutamide or abiraterone. The findings were striking, none of the...

Multiple mechanisms of resistance contribute to the inevitable progression of hormone-sensitive prostate cancer to castration-resistant prostate cancer (CRPC). Currently approved therapies for CRPC include systemic chemotherapy (docetaxel and cabazitaxel) and agents targeting the resistance pathways leading to CRPC, including enzalutamide and abiraterone. While there is significant survival ben...

Failure of androgen-targeted therapy and progression of castration-resistant prostate cancer (CRPC) are often attributed to sustained expression of the androgen receptor (AR) and its major splice variant, AR-v7. Although the new generation of anti-androgens such as enzalutamide effectively inhibits AR activity, accumulating pre-clinical and clinical evidence indicates that AR-v7 remains constit...

Prostate cancer is the main cause of cancer-related mortality among men. And although surgery and radiation have been successful treatments, between 30% and 40% of prostate cancer patients progress to advanced forms of the disease.1 Almost all patients with metastatic prostate cancer go on to develop castration-resistant prostate cancer (CRPC).2 From2004 to 2010, docetaxel-based chemotherapywas...