[The treatment of castration-resistant prostate cancer]

The last several years have seen extraordinary progress in the management of patients with castration resistant prostate cancer (CRPC). Although metastatic prostate cancer remains an incurable disease, substantial advances have been made in therapeutic options. Development of novel agents that modulate the androgen receptor pathway, growth factor signalling pathways, and immune function and bone targeting pathways has been the focus of therapeutic strategies because of its significance in the biology of prostate cancer progression. In 2004, docetaxel/prednisone was the first therapy shown to prolong survival. For the next 6 years, no substantial progress was made in prolonging survival, but the latest 2 years have marked the beginning of a new and exciting era for the treatment of mCRPC. Based on phase III clinical trials cabazitaxel, abiraterone acetate, sipuleucel-T and denosumab represent available therapeutic options in this setting, radium-223 chloride and MDV3100 demonstrated a survival advantage in phase III trials and the road for their introduction in clinical practice is rapidly ongoing. Results are also awaited for phase III studies currently underway or planned with new drugs given as monotherapy (TAK-700, cabozantinib, tasquinimod, PROSTVAC-VF, ipilimumab) or in combination with docetaxel (custirsen, aflibercept, dasatinib, zibotentan), while other emerging molecules have shown hopeful results. The aim of this review is to summarize the most important new findings for metastatic CRPC (mCRPC) according to the different molecular pathways and to discuss their potential influence on future management of this disease.