Journal article
HSD3B1(1245A>C) variant regulates dueling abiraterone metabolite effects in prostate cancer
Mohammad Alyamani, Hamid Emamekhoo, Sunho Park, Jennifer Taylor, Nima Almassi, Sunil Upadhyay, Allison Tyler, Michael P Berk, Bo Hu, Tae Hyun Hwang, William Douglas Figg, Cody J Peer, Caly Chien, Vadim S Koshkin, Prateek Mendiratta, Petros Grivas, Brian Rini, Jorge Garcia, Richard J Auchus, Nima Sharifi
JOURNAL OF CLINICAL INVESTIGATION | AMER SOC CLINICAL INVESTIGATION INC | Published : 2018
DOI: 10.1172/JCI98319
Abstract
BACKGROUND: A common germline variant in HSD3B1(1245A>C) encodes for a hyperactive 3β-hydroxysteroid dehydrogenase 1 (3βHSD1) missense that increases metabolic flux from extragonadal precursor steroids to DHT synthesis in prostate cancer. Enabling of extragonadal DHT synthesis by HSD3B1(1245C) predicts for more rapid clinical resistance to castration and sensitivity to extragonadal androgen synthesis inhibition. HSD3B1(1245C) thus appears to define a subgroup of patients who benefit from blocking extragonadal androgens. However, abiraterone, which is administered to block extragonadal androgens, is a steroidal drug that is metabolized by 3βHSD1 to multiple steroidal metabolites, including 3-..
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Awarded by National Cancer Institute
Awarded by NATIONAL CANCER INSTITUTE
Funding Acknowledgements
This work was supported in part by funding from a Prostate Cancer Foundation Challenge Award (to NS) and grants from the National Cancer Institute (R01CA168899, R01CA172382, and R01CA190289 to NS).