Perspectives on the current and emerging chemical androgen receptor antagonists for the treatment of prostate cancer.

INTRODUCTION:  Prostate cancer is the most common cancer in men. Regardless of the initial treatment of localized disease, almost all patients develop castration resistant prostate cancer (CRPC). A better understanding of the molecular mechanisms behind castration resistance has led to the approval of novel oral androgen receptor (AR) antagonists, such as enzalutamide and apalutamide. Indeed, research has accelerated with numerous agents being studied for the management of CRPC. Areas covered: Herein, the authors present currently used and emerging AR antagonists for the treatment of CRPC. Emerging agents include darolutamide, EZN-4176, AZD-3514, and AZD-5312, apatorsen, galeterone, ODM-2014, TRC-253, BMS-641988, and proxalutamide. Expert opinion: Further understanding of the mechanisms leading to castration resistance in prostate cancer can reveal potential targets for the development of novel AR antagonists. Current novel agents are associated with modest clinical and survival benefit, while acquired resistance and safety issues are under continuous evaluation. The combination of AR antagonists used and ideal sequencing strategies are key tasks ahead, along with the investigation of molecular biomarkers for future personalized targeted therapies. In the future, the challenge will be to determine an AR antagonist with the best combination of outcome and tolerability.