Castration‐Resistant Prostate Cancer: Targeted Therapies and Individualized Treatment

Various molecular mechanisms have been implicated in the progression from hormone‐sensitive to castration‐resistant prostate cancer (CRPC). Novel targeted agents to treat CRPC have been developed that inhibit either androgen receptor (AR)‐mediated signaling (AR antagonists and inhibitors of androgen synthesis) or non–AR‐mediated signaling (inhibitors of Src, mammalian target of rapamycin, chaperone proteins, insulin‐like growth factor‐1 receptor, vascular endothelial growth factor, and endothelin‐A receptor) pathways. However, variable efficacy has been observed in clinical trials, most likely because of the biologic heterogeneity of CRPC. To account for potential differences in disease biology, a more individualized approach to treatment, based on genomic and/or proteomic analyses of individual tumors, is being investigated. By identifying tumors with a characteristic molecular subtype and assigning treatment accordingly, it is hoped that a higher proportion of patients will benefit from targeted therapy. Additionally, lessons learned through the application of these technologies to prostate cancer may subsequently influence therapeutic development in other solid tumors.