Resistance to CYP17A1 Inhibition with Abiraterone in Castration-Resistant Prostate Cancer: Induction of Steroidogenesis and Androgen Receptor Splice Variants
Beth Israel Deaconess Medical Center · University of Washington · +4 more institutions
Abstract
PURPOSE: Abiraterone is a potent inhibitor of the steroidogenic enzyme CYP17A1 and suppresses tumor growth in patients with castration-resistant prostate cancer (CRPC). The effectiveness of abiraterone in reducing tumor androgens is not known, nor have mechanisms contributing to abiraterone resistance been established. EXPERIMENTAL DESIGN: We treated human CRPC xenografts with abiraterone and measured tumor growth, tissue androgens, androgen receptor (AR) levels, and steroidogenic gene expression versus controls. RESULTS: Abiraterone suppressed serum PSA levels and improved survival in two distinct CRPC xenografts: median survival of LuCaP35CR improved from 17 to 39 days (HR = 3.6, P = 0.0014) and LuCaP23CR…
Citation impact
- FWCI
- 48.42
- Percentile
- 100%
- References
- 42
Authors
8- EAElahe A. MostaghelCorresponding
Beth Israel Deaconess Medical Center, University of Washington, Fred Hutch Cancer Center, VA Puget Sound Health Care System, Cancer Research Center
- BTBrett T. Marck
Beth Israel Deaconess Medical Center, Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa, University of Washington, Fred Hutch Cancer Center, VA Puget Sound Health Care System, Cancer Research Center
- SRStephen R. Plymate
Beth Israel Deaconess Medical Center, University of Washington, Fred Hutch Cancer Center, VA Puget Sound Health Care System, Cancer Research Center
- RLRobert L. Vessella
Beth Israel Deaconess Medical Center, Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa, University of Washington, Fred Hutch Cancer Center, VA Puget Sound Health Care System, Cancer Research Center
- SBStephen Balk
Beth Israel Deaconess Medical Center, Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa, University of Washington, Fred Hutch Cancer Center, VA Puget Sound Health Care System, Cancer Research Center
Topics & keywords
- CYP17A1
- Prostate cancer
- Androgen receptor
- Abiraterone
- Testosterone (patch)
- Endocrinology
- Internal medicine
- Androgen
- Good health and well-being