title: CYP17 inhibitors for prostate cancer therapy.
abstract: Prostate cancer (PC) is now the second most prevalent cause of death in men in the USA and Europe. At present, the major treatment options include surgical or medical castration. These strategies cause ablation of the production of testosterone (T), dihydrotestosterone (DHT) and related androgens by the testes. However, because these procedures do not affect adrenal, prostate and other tissues' androgen production, they are often combined with androgen receptor antagonists to block their action. Indeed, recent studies have unequivocally established that in castration-resistant prostate cancer (CRPC) many androgen-regulated genes become re-expressed and tissue androgen levels increase despite low serum levels. Clearly, inhibition of the key enzyme which catalyzes the biosynthesis of androgens from pregnane precursors, 17α-hydroxy/17,20-lyase (hereafter referred to as CYP17) could prevent androgen production from all sources. Thus, total ablation of androgen production by potent CYP17 inhibitors may provide effective treatment of prostate cancer patients. This review highlights the role of androgen biosynthesis in the progression of prostate cancer and the impact of CYP17 inhibitors, such as ketoconazole, abiraterone acetate, VN/124-1 (TOK-001) and TAK-700 in the clinic and in clinical development. Article from the special issue on Targeted Inhibitors.
authors.affiliation: Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Tadas S
authors.initials: TS
authors.lastname: Vasaitis
authors.forename: Robert D
authors.initials: RD
authors.lastname: Bruno
authors.forename: Vincent C O
authors.initials: VC
authors.lastname: Njar
mesh_terms: D000728:Androgens / Q000096:biosynthesis* / Q000737:chemistry; D002986:Clinical Trials as Topic; D018450:Disease Progression; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D015394:Molecular Structure; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000201:enzymology*; D011944:Receptors, Androgen / Q000378:metabolism; D013254:Steroid 17-alpha-Hydroxylase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D000728:Androgens; D004791:Enzyme Inhibitors; D011944:Receptors, Androgen; D013254:Steroid 17-alpha-Hydroxylase