CYP17 inhibitors for prostate cancer treatment--an update.
It is almost 70 years since the discovery by Huggins et al. that androgens are essential for prostate cancer (PC) growth and progression, and there has been about 30 years experience using ketoconazole for PC therapy. Since then we have come a long way in learning about the disease and developing new strategies to approach it, among which is cytochrome 17alpha-hydroxylase-C(17,20)-lyase (CYP17) inhibition. This review focuses on the efforts to find prospective CYP17 inhibitors, both steroidal and nonsteroidal, in the absence of a 3D structure of the enzyme. It covers almost 4 decades of literature with highlights on the most significant achievements in this area, providing insight into PC pathophysiology, management and treatment options.
Moreira
V M
VM
Laboratório de Química Farmacêutica, Faculdade de Farmácia, Universidade de Coimbra, Rua do Norte, 3000-295 Coimbra, Portugal.
Salvador
J A R
JA
Vasaitis
T S
TS
Njar
V C O
VC
D000728:Androgens / Q000737:chemistry / Q000378:metabolism; D000731:Androstanes / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use*; D006801:Humans; D007093:Imidazoles / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D008297:Male; D011278:Pregnanes / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D011725:Pyridines / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D013254:Steroid 17-alpha-Hydroxylase / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000728:Androgens; D000731:Androstanes; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D007093:Imidazoles; D011278:Pregnanes; D011725:Pyridines; D013254:Steroid 17-alpha-Hydroxylase