title: Androgen receptor directed therapies in castration-resistant metastatic prostate cancer.
abstract: Recent results of phase III randomized studies confirm that targeting the androgen receptor (AR)-through inhibition of androgen synthesis or through AR targeting directly-can improve survival for patients with metastatic castration-resistant prostate cancer (mCRPC), a condition previously considered to be "refractory" to further hormonal manipulation. These data validate in the clinical setting much of the scientific work of the previous decade that has demonstrated the extent of and mechanisms behind retained AR signaling in advanced prostate cancer. The convergence of these observations effectively changes the perspective with which androgen deprivation is utilized in prostate cancer, and forms the basis for further expansion of systemic therapy in the disease. In this review, the rationale for and clinical results with these new therapies will be discussed as will the future directions required to fully leverage these therapeutic modalities to the maximum clinical benefit for patients.
authors.affiliation: Genitourinary Medical Oncology Program, UCSF Helen Diller Family Comprehensive Cancer Center, 1600 Divisadero Street, San Francisco, CA 94115, USA. won.kim@ucsf.edu
authors.forename: Won
authors.initials: W
authors.lastname: Kim
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Ryan
mesh_terms: D059002:Androgen Receptor Antagonists / Q000627:therapeutic use*; D000736:Androstenes; D000737:Androstenols / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D001549:Benzamides; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007654:Ketoconazole / Q000627:therapeutic use; D008297:Male; D009570:Nitriles; D009919:Orchiectomy; D010669:Phenylthiohydantoin / Q000031:analogs & derivatives / Q000627:therapeutic use; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D011944:Receptors, Androgen / Q000378:metabolism*; D013254:Steroid 17-alpha-Hydroxylase / Q000037:antagonists & inhibitors; D043823:Taxoids / Q000627:therapeutic use; D013867:Thiohydantoins / Q000627:therapeutic use
chemical_list: D059002:Androgen Receptor Antagonists; D000736:Androstenes; D000737:Androstenols; D000970:Antineoplastic Agents; D018931:Antineoplastic Agents, Hormonal; D001549:Benzamides; D009570:Nitriles; D011944:Receptors, Androgen; D043823:Taxoids; D013867:Thiohydantoins; C572045:apalutamide; D000077143:Docetaxel; D010669:Phenylthiohydantoin; C540278:enzalutamide; D013254:Steroid 17-alpha-Hydroxylase; C089740:abiraterone; D007654:Ketoconazole