Castration-Resistant Prostate Cancer

Men with advanced prostate cancer are typically treated with hormonal therapy, which results in tumor shrinkage. However, tumors relapse and develop into a highly aggressive and lethal form of the disease, termed castration-resistant prostate cancer (CRPC). Evidence suggests that tumor cells acquire new genetic and epigenetic alterations that enable them to survive in the castrated state. Yet, it has recently emerged that immune cells in the tumor microenvironment and a population of rare, pre-existing cancer stem cells can also facilitate the outgrowth of CRPC following hormonal therapy. Targeting the cells that survive therapy is principal to prevent the development of CRPC. This chapter will describe the molecular identity of CRPC and the cellular mechanisms employed by prostate cancer cells that drive progression to this lethal phase of prostate cancer. The treatment of CRPC is reviewed, with a focus on emerging therapeutic strategies targeting critical pathways in castration-resistant cancer cells.