Nonhormone therapy for metastatic castration-resistant prostate cancer: chemotherapy, bone-targeted treatments, and others.

OVERVIEW There is no doubt that more therapeutic progress has been achieved during the last 3 years for patients with metastatic castrationresistant prostate cancer (mCRPC) than during the previous 30 years. During this limited time frame, not only have six compounds (sipuleucel-T, cabazitaxel, denosumab, abiraterone, radium-223, and enzalutamide, listed in chronologic order) yielded positive results in phase III trials, we have also learned that their mechanisms of action are different, making it quite likely that part of their anticancer activity may be incremental. Most of these agents have already been approved. Further progress may well soon complete this recently enlarged armamentarium, with important trials testing new agents derived from existing families of compounds (new endocrine therapies, new immunotherapies, etc.) and exploring the activity of new families of agents (tyrosine kinase inhibitors such as cabozantinib, inhibitors of chaperone proteins like OGX-O11 and OGX-427). The availability of these agents creates a new major challenge for those who conduct clinical research in mCRPC. Will we be able to personalize therapy based on the biology of the individual’s tumor, as we are already doing in other neoplasms?