Inhibition of EZH2 transactivation function sensitizes solid tumors to genotoxic stress

Abstract

We identified a group of DNA repair genes directly induced by EZH2 and repressed by EZH2 inhibitors. Expression of these genes predicts the response of wild-type EZH2-harboring solid tumors to EZH2 inhibitors. Most importantly, our findings lay the foundation for the development of a combination therapy that combines EZH2 inhibitors and DNA damaging agents or drugs that block DNA repair for the treatment of castration-resistant prostate cancer and other solid tumors.

Document Details

Document Type
Pub Defense Publication
Publication Date
Jan 14, 2022
Source ID
10.1073/pnas.2105898119

Entities

People

  • Avery Feit
  • Bárbara De La Peña Avalos
  • Changmeng Cai
  • Chen-hao Chen
  • Eloise Dray
  • Han Xu
  • Henry Long
  • James E. Bradner
  • Ji Hoon Lee
  • Jin Zhao
  • Kexin Xu
  • Kornélia Polyák
  • Mei Yang
  • Melissa Duarte
  • Myles A. Brown
  • Neel J. Shah
  • Pengya Xue
  • Philip W. Kantoff
  • Roodolph S. Pierre
  • Shaokun Shu
  • Shenglin Mei
  • Shuai Gao
  • Steven P Balk
  • Teng Fei
  • Tengfei Xiao
  • Wei Li
  • Xiaole Shirley Liu
  • Yiji Liao
  • Zhao Zhang
  • Zhijie Liu

Organizations

  • American Association for Cancer Research
  • Beth Israel Deaconess Medical Center
  • Cancer Prevention and Research Institute of Texas
  • Dana–Farber Cancer Institute
  • Harvard Medical School
  • Harvard University
  • Max and Minnie Tomerlin Voelcker Fund
  • National Cancer Institute
  • National Human Genome Research Institute
  • Prostate Cancer Foundation
  • United States Department of Defense
  • University of Massachusetts
  • University of Texas Health Science Center at San Antonio

Tags

Fields of Study

  • Biology

Readers

  • Molecular Biology and Genetics
  • Molecular and genetic basis of cancer.
  • Prostate Cancer Biology.

Technology Areas

  • Biotechnology