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, 17alpha-
hydroxylase/
17,20-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 pharmaceutical industry. This review highlights development in the design and evaluation of both steroidal and non-steroidal
CYP17 inhibitors since 1965. Major emphasis is given to the potent
CYP17 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.