Activity of VT-464, a selective CYP17 lyase inhibitor, in the LNCaP prostate cancer xenograft model.
- Stephen Todd Pisle,
- Heather M Pressler,
- Sarah M Troutman,
- Joel Robert Eisner,
- Stephen W Rafferty,
- Robert J Schotzinger,
- William R Moore,
- William Douglas Figg
J Clin Oncol 2012 Feb;30(5_suppl):64
Clinical Pharmacology Program, SAIC-Frederick, Bethesda, MD; Molecular Pharmacology Section, National Cancer Institute, National Institutes of Health, Bethesda, MD; National Cancer Institute, Bethesda, MD; Viamet Pharmaceuticals, Inc., Morrisville, NC.
64 Background: With the recent FDA approval of abiraterone acetate, CYP17 (17α hydroxylase/C17, 20-lyase) has become a proven target for the treatment of castration- resistant prostate cancer. Inhibition of CYP17-lyase causes a decrease in circulating androgens, severely hampering activation of the androgen receptor signaling pathway that prostate cancer relies on for proliferation. However, inhibition of CYP17-hydroxylase, a second enzymatic activity of CYP17, leads to an increase in upstream steroids that can cause mineralocorticoid excess syndrome as well as a decrease in cortisol production. Read More