Castration-Resistant Prostate Cancer: Novel Targets, Agents, and Trials

摘要

The therapeutic landscape for men with castration-resistant prostate cancer (CRPC) has changed dramatically with recent U.S. Food and Drug Administration (FDA) approvals of sipuleucel-T, cabazitaxel, abiraterone, and denosumab. Each agent has a distinct mechanism of action, with effects ranging from cytotoxicity, immune modulation, hormonal manipulation, and bone turnover. Yet, many other drugs attenuating new biologic targets are in clinical trials. In prostate cancer, measures of tumor angiogenesis (i.e., microvessel density and vascular endothelial growth factor [VEGF] levels) correlate with metastatic disease, Gleason grade, and clinical outcome. However, antiangiogenic agents have yet to prove an overall survival (OS) benefit for men with prostate cancer. Recently, bevacizumab (a monoclonal antibody to VEGF) and sunitinib (a kinase inhibitor of VEGFR-1, -2, and -3) both yielded improvements in progression-free survival (PFS), but not OS.