Inhibitors of 17α-Hydroxylase/17,20-Lyase (CYPl7): Potential Agents for the Treatment of Prostate Cancer

Abstract

Prostate cancer (PCa) is now the most prevalent cancer in men in the U.S.A. and Europe. At present the major treatment options include surgical or medical castration. These strategies depend on the abolition of the production of testosterone by the testes. However, as these procedures do not affect adrenal androgen production, they are frequently combined with androgen receptor antagonist to block their action. Inhibition of the key enzyme which catalyzes the biosynthesis of androgens from pregnane precursors, I 7a­ hydroxylase/l 7,20-lyase (hereafter referred to as CYP17 ) could prevent androgen biosynthesis from both sources. Thus total blockade of androgen production by CYP17 inhibitors may provide effective treatment of prostate cancer patients. Indeed, this strategy is now an area of intense interest within research institutions and the pharmaceulical industry. This review highlights development in the design and evaluation of both steroidal and non-steroidal CYPl 7 inhibitors since 1965. Major emphasis is given to the potent CYPI 7 inhibitors and those which may show clinical promise. The review could function as a comprehensive working reference of research accomplishment in the field and what problems remain to be tackled in the future.