BET Bromodomain Inhibition Blocks an AR-Repressed, E2F1-Activated Treatment-Emergent Neuroendocrine Prostate Cancer Lineage Plasticity Program
Abstract
Lineage plasticity in prostate cancer—most commonly exemplified by loss of androgen receptor (AR) signaling and a switch from a luminal to alternate differentiation program—is now recognized as a treatment resistance mechanism. Lineage plasticity is a spectrum, but neuroendocrine prostate cancer (NEPC) is the most virulent example. Currently, there are limited treatments for NEPC. Moreover, the incidence of treatment-emergent NEPC (t-NEPC) is increasing in the era of novel AR inhibitors. In contradistinction to de novo NEPC, t-NEPC tumors often express the AR, but AR's functional role in t-NEPC is unknown. Furthermore, targetable factors that promote t-NEPC lineage plasticity are also unclear.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jun 18, 2021
- Source ID
- 10.1158/1078-0432.ccr-20-4968
Entities
People
- Anbarasu Kumaraswamy
- Armand Bankhead Iii
- Arvind Rao
- Chao Zhang
- Chelsea Jenkins
- Colm Morrissey
- Dae‐Hwan Kim
- Daniel E. Spratt
- Daniel J. Coleman
- David Sampson
- Duanchen Sun
- Emily M. Gesner
- Eric Campeau
- Eric J Small
- Eva Corey
- Eva S. Rodansky
- Felix Y. Feng
- Himisha Beltran
- Ilsa M. Coleman
- Jacob Schwartzman
- Jared M. Lucas
- Joel A Yates
- Jonathan Z Sexton
- Joshi J Alumkal
- Joshua Urrutia
- Katherine Welker Leng
- Mark P Labrecque
- Peter S Nelson
- Rahul Aggarwal
- Samuel K. Handelman
- Sanjay Lakhotia
- Sarah Attwell
- Wassim Abida
- William K. Storck
- Xiangnan Guan
- Zheng Xia
Organizations
- Case Western Reserve University
- Fred Hutchinson Cancer Center
- Harvard Medical School
- Memorial Sloan Kettering Cancer Center
- National Cancer Institute
- Oregon Health & Science University
- University of California, San Francisco
- University of Michigan
- University of Washington