CYP17 inhibitors for prostate cancer therapy.

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Vasaitis TS, Bruno RD, Njar VC

CYP17 inhibitors for prostate cancer therapy.

J Steroid Biochem Mol Biol. 2011 May;125(1-2):23-31. doi: 10.1016/j.jsbmb.2010.11.005. Epub 2010 Nov 17.

PubMed ID

21092758 [ View in PubMed

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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, 17alpha-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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Progesterone	Steroid 17-alpha-hydroxylase/17,20 lyase	Protein	Humans	Unknown	Substrate Inhibitor	Details