title: Galeterone for the treatment of advanced prostate cancer: the evidence to date.
abstract: Major advances have been achieved recently in the treatment of metastatic castration-resistant prostate cancer, resulting in significant improvements in quality of life and survival with the use of several new agents, including the next-generation androgen receptor (AR)-targeted drugs abiraterone and enzalutamide. However, virtually all patients will eventually progress on these therapies and most will ultimately die of treatment-refractory metastatic disease. Recently, several mechanisms of resistance to AR-directed therapies have been uncovered, including the AR splice variant 7 (AR-V7), which is a ligand-independent constitutionally-active form of the AR that has been associated with poor outcomes to abiraterone and enzalutamide. Galeterone, a potent anti-androgen with three modes of action (CYP17 lyase inhibition, AR antagonism, and AR degradation), is a novel agent under clinical development that could potentially target both full-length AR and aberrant AR, including AR-V7. In this manuscript, we will first discuss the biological mechanisms of action of galeterone and then review the safety and efficacy data from Phase I and II clinical studies of galeterone in patients with metastatic castration-resistant prostate cancer. A Phase III study of galeterone (compared against enzalutamide) in AR-V7-positive patients is currently underway, and represents the first pivotal trial using a biomarker-selection design in this disease.
authors.affiliation: Department of Oncology, Hospital Sirio-Libanes, Sao Paulo, Brazil.
authors.forename: Diogo A
authors.initials: DA
authors.lastname: Bastos
authors.affiliation: Department of Oncology and Urology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Emmanuel S
authors.initials: ES
authors.lastname: Antonarakis
mesh_terms: D000730:Androstadienes / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism
chemical_list: C410798:AR protein, human; D000730:Androstadienes; D000970:Antineoplastic Agents; D001562:Benzimidazoles; D011944:Receptors, Androgen; C500627:3-hydroxy-17-(1H-benzimidazole-1-yl)androsta-5,16-diene
keywords: AR splice variants; AR-V7; castration-resistant prostate cancer; galeterone