title: Novel and next-generation androgen receptor-directed therapies for prostate cancer: Beyond abiraterone and enzalutamide.
abstract: The approval of abiraterone and enzalutamide for the treatment of advanced castration-resistant prostate cancer heralded a paradigm shift in the management of this disease. Nevertheless, new and improved treatments are needed since the disease remains incurable for the majority of these patients. In this article, we review the biology of castration-resistant disease as well as emerging therapeutic compounds directed at the androgen receptor, including galeterone, VT-464, ARN-509, and ODM-201. Mechanisms of action, early clinical data, and ongoing clinical studies for these compounds are all reviewed. The need to find optimal sequencing and combination strategies as well as the need for predictive biomarkers of response to these agents is discussed.
authors.affiliation: GU Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY. Electronic address: richardbambury@icloud.com.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Bambury
authors.affiliation: GU Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Dana E
authors.initials: DE
authors.lastname: Rathkopf
mesh_terms: D059002:Androgen Receptor Antagonists / Q000627:therapeutic use*; D000730:Androstadienes / Q000627:therapeutic use; D000736:Androstenes / Q000627:therapeutic use*; D001549:Benzamides; D001562:Benzimidazoles / Q000627:therapeutic use; D006801:Humans; D008297:Male; D009281:Naphthalenes / Q000627:therapeutic use; D009570:Nitriles; D010669:Phenylthiohydantoin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy*; D011720:Pyrazoles / Q000627:therapeutic use; D011944:Receptors, Androgen; D013867:Thiohydantoins / Q000627:therapeutic use; D014230:Triazoles / Q000627:therapeutic use
chemical_list: D059002:Androgen Receptor Antagonists; D000730:Androstadienes; D000736:Androstenes; D001549:Benzamides; D001562:Benzimidazoles; D009281:Naphthalenes; D009570:Nitriles; D011720:Pyrazoles; D011944:Receptors, Androgen; D013867:Thiohydantoins; D014230:Triazoles; C000601472:VT-464; C572045:apalutamide; C000607739:darolutamide; D010669:Phenylthiohydantoin; C540278:enzalutamide; C089740:abiraterone; C500627:3-hydroxy-17-(1H-benzimidazole-1-yl)androsta-5,16-diene
keywords: ARN-509; Bipolar androgen therapy; Castration-resistant prostate cancer; Galeterone; ODM-201; VT-464