Estrogen-regulated feedback loop limits the efficacy of estrogen receptor–targeted breast cancer therapy
Abstract
Estrogen receptor-positive (ER + ) breast cancer is treated with endocrine therapies, although therapeutic resistance almost invariably develops in advanced disease. Using genome-wide CRISPR screens, we identified genes whose loss confers endocrine resistance, as well as synthetic lethal vulnerabilities to overcome such resistance. These findings reveal an estrogen-induced negative feedback loop that constrains the growth of ER + tumors, thereby limiting the efficacy of therapies that inhibit ER, and suggest a previously unappreciated therapeutic route to overcoming endocrine resistance.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jul 09, 2018
- Source ID
- 10.1073/pnas.1722617115
Entities
People
- Chongzhi Zang
- David Chi
- Eran R Andrechek
- Han Xu
- Jixin Yang
- Jonathan Rennhack
- Joseph Geradts
- Mitchell Dowsett
- Myles A. Brown
- Nanlin Li
- Peng Jiang
- Qi Liao
- Qiu Wu
- Rinath M. Jeselsohn
- Simone Detre
- Teng Fei
- Tengfei Xiao
- Wei Li
- Xiaole Shirley Liu
- Xiaoqing Wang
- Ying Huang
Organizations
- Air Force Medical University
- Children's National Hospital
- Dana–Farber Cancer Institute
- George Washington University Medical School
- Harvard Medical School
- Harvard University
- Institute of Cancer Research
- Michigan State University
- National Institutes of Health
- Ningbo University
- Northeastern University
- Susan G. Komen for the Cure
- The Breast Cancer Research Foundation
- Tongji University
- United States Department of Defense