Over the next ten years, more than 15 million men worldwide will be diagnosed with prostate cancer, resulting in nearly 3 million first-line drug-treatment opportunities in the metastatic castrate-resistant prostate cancer (mCRPC) setting (1,2 ). The biomarker prostate-specific antigen (PSA) is commonly used to screen for men with prostate cancer, though some challenges exist over diagnosing patients with cancer based on this screen. The development of biomarkers for oncology indications has grown at an exponential rate, allowing for the identification of disease, prediction of disease progression, prognosis and even therapeutic choice. Stratification of prostate cancer patients using biomarkers predictive of response to therapy is somewhat lacking.

  • Much work is underway to investigate the biology of advanced prostate cancer and many of these studies point towards the involvement of the Androgen Receptor (AR) signalling pathway in resistance to current anti-AR treatments available (Johnson&Johnson / Janssen Biotech / Janssen-Cilag / AstraZeneca’s Zytiga [abiraterone] and Medivation / Astellas Pharma’s Xtandi [enzalutamide]).
  • The splice variant AR-V7 can be detected in circulating tumor cells (CTCs) in the blood and has been associated with drug resistance. Data presented by E.S. Antonarakis at ASCO 2016 indicated that positive detection of AR-V7 in CTCs in patients with prostate cancer was sufficient to predict poor prognosis compared with those that did not have the splice variant.
  • The AR-V7-positive patients identified in this study failed to respond to the anti-AR agents, abiraterone and enzalutamide, which are the standard of care for the treatment of mCRPC. Overall, the AR-V7-positive patients had a shorter overall survival (11.2 vs. 29.5 months, p<0.001) and progressed much faster (3.1 vs. 7.7 months, p<0.001) than patients that were AR-V7–negative (3,4). The AR-V7-positive patients when treated with taxane chemotherapy instead of anti-AR therapy survived much longer (8.9 vs. 4.6 months, p<0.001) (3,4).

Overall this shows that AR-V7 detection in CTCs could be a new predictive test to allow patients with mCRPC to be screened prior to treatment, thereby avoiding unnecessary treatment with expensive and ineffective therapies over cheaper chemotherapeutic agents which are more likely to be effective.

Tokai Pharmaceuticals’ galeterone (TOK-001) is a multi-targeted novel hormonal agent that entered Phase III development for mCRPC patients who are AR-V7-positive in June 2015. The agent has been granted FDA fast-track designation for mCRPC and Tokai is collaborating with Qiagen to develop an assay for AR-V7 on CTCs (Tokai Pharmaceuticals, press release, June 24, 2015).

At present the identification and validation of predictive biomarkers to improve patient selection is a key unmet need for prostate cancer (5,6). If the Phase III trial is positive, galeterone would become the first biomarker-driven therapy to enter the prostate cancer treatment armamentarium, which would differentiate it from the other anti-AR therapies available.


  1. Global Forecast of the Coming Ten Years in the Epidemiology and Treatment Opportunities for Prostate Cancer. Decision Resources Group. October 2015 
  2. Epidemiology. Prostate Cancer. Decision Resources Group.  
  3. Antonarakis ES, et al. AR-V7 and efficacy of abiraterone (Abi) and enzalutamide (Enza) in castration-resistant prostate cancer (CRPC): Expanded analysis of the Johns Hopkins cohort.J Clin Oncol 34, 2016 (suppl; abstract 5012)
  4. Scher, H et al. Association of AR-V7 on Circulating Tumor Cells as a Treatment-Specific Biomarker With Outcomes and Survival in Castration-Resistant Prostate Cancer. JAMA Oncology. Advance Online Publication: June 4, 2016. DOI:10.1001/jamaoncol.2016.1828
  5. Prostate Cancer | Disease Landscape and Forecast | G7. Decision Resources Group. January 2016 
  6. Prostate Cancer | Unmet Need | US/EU. Decision Resources Group. January 2016.  




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