Transcriptional profiling identifies an androgen receptor activity-low, stemness program associated with enzalutamide resistance
Abstract
The androgen receptor (AR) antagonist enzalutamide is one of the principal treatments for men with metastatic castration-resistant prostate cancer. However, not all patients respond, and de novo resistance mechanisms are largely unknown. To clarify mechanisms that contribute to enzalutamide resistance, we conducted a single-arm enzalutamide clinical trial. Metastatic tissue biopsies were required prior to study entry so we could attempt to identify molecular features associated with de novo resistance. Transcriptional profiling identified specific gene sets—including those linked to reduced AR transcriptional activity and a stemness program—that were activated in nonresponders. Our results suggest that patients whose tumors harbor this program should be considered for clinical trials testing rational agents to overcome de novo enzalutamide resistance.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- May 18, 2020
- Source ID
- 10.1073/pnas.1922207117
Entities
People
- Adam Foye
- Alana S Weinstein
- Charles J Ryan
- Christopher P Evans
- Claire B. Turina
- Daniel E. Spratt
- David A. Quigley
- Duanchen Sun
- Emile Latour
- Eric J Small
- Eric Lu
- Felix Y. Feng
- George V Thomas
- Jack F. Youngren
- Jeremy Cetnar
- Jiaoti Huang
- Joshi J Alumkal
- Joshua M Stuart
- Joshua Urrutia
- Martin Gleave
- Matthew B Rettig
- Owen N Witte
- Rahul Aggarwal
- Robert E. Reiter
- Shaadi Tabatabaei
- Shawna Bailey
- Tomasz M Beer
- Verena Friedl
- Xiangnan Guan
- Yiyi Chen
- Zheng Xia
Organizations
- Duke University
- National Cancer Institute
- Stand Up to Cancer
- United States Department of Defense
- University of British Columbia
- University of California
- University of California, Los Angeles
- University of California, San Francisco
- University of California, Santa Cruz
- University of Michigan
- University of Michigan Rogel Cancer Center
- University of Minnesota
- VA Greater Los Angeles Healthcare System