Inhibitors of 17 alpha-hydroxylase/17,20-lyase (CYP17): Potential agents for the treatment of prostate cancer

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 med ical 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 rec eptor antagonist to block their action. Inhibition of the key enzyme which catalyzes the biosynthesis of androgens from pregnane precursors, 17 alpha-hydroxylase/17,70-lyase (hereafter refer red to as CYP17) could prevent androgen biosynthesis from both sources. Thu s total blockade of androgen production by CYP17 inhibitors may provide eff ective treatment of prostate cancer patients. Indeed, this strategy is now an area of intense interest within research institutions and the pharmaceut ical industry. This review highlights development in the design and evaluat ion of both steroidal and non-steroidal CYP17 inhibitors since 1965. Major emphasis is given to the potent CYP17 inhibitors and those which may show c linical promise. The review could function as a comprehensive working refer ence of research accomplishment in the field and what problems remain to be tackled in the future.