TY - JOUR
T1 - Targeting CYP17
T2 - established and novel approaches in prostate cancer
AU - Yap, Timothy A.
AU - Carden, Craig P.
AU - Attard, Gerhardt
AU - de Bono, Johann S.
PY - 2008/8/1
Y1 - 2008/8/1
N2 - There is a growing body of evidence that although medical or surgical castration blocks the generation of gonadal testosterone in prostate cancer, androgens originating from other sources may continue to drive androgen receptor (AR) signaling. Recent studies have demonstrated high intratumoral levels of androgens and continued AR signaling in castration-resistant prostate cancer (CRPC), suggesting that androgens may also be synthesized de novo. Inhibiting the systemic biosynthesis of androgens in CRPC by targeting CYP17 may thus represent a rational therapeutic approach since this enzyme catalyses two key steroid reactions involving 17α-hydroxylase and C17,20-lyase in the androgen biosynthesis pathway. This review will discuss the rationale for and implications of targeting CYP17 in CRPC and focus on established and novel CYP17 inhibitors, including ketoconazole, abiraterone acetate, and VN/124-1, which are agents currently at different stages of development.
AB - There is a growing body of evidence that although medical or surgical castration blocks the generation of gonadal testosterone in prostate cancer, androgens originating from other sources may continue to drive androgen receptor (AR) signaling. Recent studies have demonstrated high intratumoral levels of androgens and continued AR signaling in castration-resistant prostate cancer (CRPC), suggesting that androgens may also be synthesized de novo. Inhibiting the systemic biosynthesis of androgens in CRPC by targeting CYP17 may thus represent a rational therapeutic approach since this enzyme catalyses two key steroid reactions involving 17α-hydroxylase and C17,20-lyase in the androgen biosynthesis pathway. This review will discuss the rationale for and implications of targeting CYP17 in CRPC and focus on established and novel CYP17 inhibitors, including ketoconazole, abiraterone acetate, and VN/124-1, which are agents currently at different stages of development.
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U2 - 10.1016/j.coph.2008.06.004
DO - 10.1016/j.coph.2008.06.004
M3 - Review article
C2 - 18619560
AN - SCOPUS:51449124047
SN - 1471-4892
VL - 8
SP - 449
EP - 457
JO - Current Opinion in Pharmacology
JF - Current Opinion in Pharmacology
IS - 4
ER -