Androgen and the androgen receptor (AR) pathway remain the key targets for 
emerging new therapies against castration-resistant prostate cancer (CRPC). 
Adrenal androgens and intratumoral testosterone production appear to be 
sufficient to activate AR in the castration-resistant setting. This process 
re-engages AR and allows it to continue to be the primary target responsible for 
prostate cancer progression. Adrenal androgen production can be blocked by 
inhibiting cytochrome P450 17α-hydroxylase/17,20-lyase (CYP17), a key enzyme for 
androgen synthesis in adrenal glands and peripheral tissues. Therapeutic CYP17 
inhibition by ketoconazole or by the recently approved adrenal inhibitor 
abiraterone acetate is the only available choice to target this pathway in CRPC. 
A new CYP17 inhibitor, with more selective inhibition of 17,20-lyase over 
17α-hydroxylase, orteronel (TAK-700), is currently undergoing phase III clinical 
trials in pre- and postchemotherapy CRPC. In a completed phase II trial in CRPC 
patients, orteronel demonstrated its efficacy by lowering the levels of 
circulating androgens, reducing prostate-specific antigen (PSA) levels, and 
decreasing the levels of circulating tumor cells. Ongoing studies evaluating 
orteronel in CRPC will further define its safety and role in the management of 
this disease.