title: CYP17A1 inhibitors in castration-resistant prostate cancer.
abstract: The majority of prostate cancer (PCa) cases are diagnosed as a localized disease. Definitive treatment, active surveillance or watchful waiting are employed as therapeutic paradigms. The current standard of care for the treatment of metastatic PCa is either medical or surgical castration. Once PCa progresses in spite of castrate androgen levels it is termed 'castration-resistant prostate cancer' (CRPC). Patients may even exhibit rising PSA levels with possible bone, lymph node or solid organ metastases. In 2010, the only agent approved for the treatment of CRPC was docetaxel, a chemotherapeutic agent. It is now known that cells from patients with CRPC express androgen receptors (AR) and remain continuously influenced by androgens. As such, treatments with novel hormonal agents that specifically target the biochemical conversion of cholesterol to testosterone have come to the forefront. The use of cytochrome P450c17 (CYP17A1) inhibitor underlies one of the most recent advances in the treatment of CRPC. Abiraterone acetate (AA) was the first CYP17A1 inhibitor approved in the United States. This review will discuss CRPC in general with a specific focus on AA and novel CYP17A1 inhibitors. AA clinical trials will be reviewed along with other novel adjunct treatments that may enhance the effectiveness of abiraterone therapy. Furthermore, the most recently identified CYP17A1 inhibitors Orteronel, Galeterone, VT-464, and CFG920 will also be explored.
authors.affiliation: Scott Department of Urology and The Center for Reproductive Medicine, and the Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, United States.
authors.forename: Lissette
authors.initials: L
authors.lastname: Gomez
authors.affiliation: Urology of Indiana, Male Reproductive Endocrinology and Surgery, Carmel, IN, United States.
authors.forename: Jason R
authors.initials: JR
authors.lastname: Kovac
authors.affiliation: Scott Department of Urology and The Center for Reproductive Medicine, and the Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, United States. Electronic address: dlamb@bcm.edu.
authors.forename: Dolores J
authors.initials: DJ
authors.lastname: Lamb
mesh_terms: D000818:Animals; D002986:Clinical Trials as Topic; D065607:Cytochrome P-450 Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D018450:Disease Progression; D055808:Drug Discovery; D006801:Humans; D008297:Male; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000378:metabolism; D013254:Steroid 17-alpha-Hydroxylase / Q000037:antagonists & inhibitors*
chemical_list: D065607:Cytochrome P-450 Enzyme Inhibitors; D013254:Steroid 17-alpha-Hydroxylase
keywords: Abiraterone; Castration resistance; Prostate cancer