title: Management of metastatic castration-resistant prostate cancer: recent advances.
abstract: Metastatic prostate cancer remains a considerable therapeutic challenge; however, advances in clinical research have resulted in five new treatments in the last 2 years. The immunotherapy sipuleucel-T, the cytotoxic cabazitaxel, the androgen biosynthesis inhibitor abiraterone acetate, the radioisotope alpharadin and the anti-androgen MDV3100 have all been shown to improve overall survival in randomized phase III studies for patients with metastatic castration-resistant prostate cancer. The therapeutic strategies of targeting androgen-receptor signalling and other key intracellular pathways involved in tumour progression and treatment resistance are yielding promising results. Agents such as the dual vascular endothelial growth factor receptor/MET inhibitor cabozantinib, the clusterin inhibitor custirsen and the Src inhibitor dasatinib have shown encouraging results in phase II studies. Novel immunotherapeutics such as prostate-specific membrane antigen-directed therapy and the anti-cytotoxic T lymphocyte-associated receptor 4 (CTLA4) antibody ipilimumab are also under investigation. Optimal methods of treatment selection, combination and sequencing have yet to be determined.
authors.affiliation: Institute of Cancer Research, Sutton, Surrey, UK.
authors.forename: Deborah
authors.initials: D
authors.lastname: Mukherji
authors.forename: Andrew
authors.initials: A
authors.lastname: Eichholz
authors.forename: Johann S
authors.initials: JS
authors.lastname: De Bono
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D008297:Male; D009362:Neoplasm Metastasis; D009919:Orchiectomy / Q000379:methods; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D016032:Randomized Controlled Trials as Topic
chemical_list: D000970:Antineoplastic Agents