Expanding androgen- and androgen receptor signaling-directed therapies for castration-resistant prostate cancer

The treatment landscape of castration-resistant prostate cancer (CRPC) has been dramatically changed over the past years with the approval of several new drugs for clinical use. These include androgen axis-targeted therapy and novel drugs with different mechanisms of action, including immunotherapy (sipuleucel-T), radiopharmaceuticals (radium-223), and chemotherapy (cabazitaxel). Based on the growing knowledge that the main driver for patients progressing on standard androgen deprivation therapy is persistent activation of the androgen receptor (AR) signaling axis, new drugs were developed and demonstrated significant efficacy in recent clinical trials, leading to the approval of abiraterone and enzalutamide in several countries. In this article, we review the most recent advances in AR-directed therapies for CRPC, promising new agents under development, cross-resistance, and mechanisms of resistance for the new-generation AR-targeted agents.