As the first in class steroid 17α-hydroxylase/C17,20-lyase (CYP17) inhibitor, 
abiraterone acetate (of which the active metabolite is abiraterone) has been 
shown to improve overall survival in patients with castration-resistant prostate 
cancer (CRPC)--in those who are chemotherapy-naive and those previously treated 
with docetaxel. Furthermore, the clinical success of abiraterone demonstrated 
that CRPC, which has previously been regarded as an androgen-independent 
disease, is still driven, at least in part, by androgens. More importantly, 
abiraterone is a 'promiscuous' drug that interacts with a number of targets, 
which dictate its clinical benefits and adverse effects profile. Besides CYP17 
inhibition, abiraterone acts as an antagonist to the androgen receptor and 
inhibits 3β-hydroxysteroid dehydrogenase--two effects that potentially 
contribute to its antitumour effects. However, the inhibition of the 
17α-hydroxylase activity of CYP17, CYP11B1 and a panel of hepatic CYP enzymes 
leads to adverse effects and toxicities that include secondary mineralocorticoid 
excess. Abiraterone is also associated with increased incidence of cardiac 
disorders. Under such circumstances, development of new CYP17 inhibitors as an 
additional line of defence is urgently needed. To achieve enhanced clinical 
benefits, new strategies are being explored that include selective inhibition of 
the C17,20-lyase activity of CYP17 and multi-targeting strategies that affect 
androgen synthesis and signalling at different points. Some of these 
strategies-including the drugs orteronel, VT-464 and galeterone--are supported 
by preclinical data and are being explored in the clinic.