Targeting metastatic castration-resistant prostate cancer: mechanisms of progression and novel early therapeutic approaches.

INTRODUCTION: Advances in clinical research have led to official approval of several new treatments for metastatic prostate cancer in the last three years: sipuleucel-T, cabazitaxel, abiraterone acetate, radium-223 and enzalutamide. Although these agents have all been shown to improve overall survival in randomized Phase III trials, metastatic castration-resistant prostate cancer (mCRPC) remains incurable. AREAS COVERED: First, the review summarizes the current literature on the biology of mCRPC. The emerging data are increasing our understanding of the mechanisms that underlie the pathogenesis of castrate resistance and where future treatment might be headed. In the second part of the review, the authors assess the future directions in disease therapy. Indeed, novel selected therapeutic approaches, including novel agents and combinatorial therapies, are showing promising early results. EXPERT OPINION: Targeting different molecular pathways in combination with immunotherapy can be a promising direction in metastatic castration prostate cancer treatment. However, several challenges still exist including elucidating the optimal use and sequencing of these new agents. There are also challenges in both the design and the interpretation of the results from clinical trials.