Nature Communications (Sep 2022)
Transcriptional profiling of matched patient biopsies clarifies molecular determinants of enzalutamide-induced lineage plasticity
- Thomas C. Westbrook,
- Xiangnan Guan,
- Eva Rodansky,
- Diana Flores,
- Chia Jen Liu,
- Aaron M. Udager,
- Radhika A. Patel,
- Michael C. Haffner,
- Ya-Mei Hu,
- Duanchen Sun,
- Tomasz M. Beer,
- Adam Foye,
- Rahul Aggarwal,
- David A. Quigley,
- Jack F. Youngren,
- Charles J. Ryan,
- Martin Gleave,
- Yuzhuo Wang,
- Jiaoti Huang,
- Ilsa Coleman,
- Colm Morrissey,
- Peter S. Nelson,
- Christopher P. Evans,
- Primo Lara,
- Robert E. Reiter,
- Owen Witte,
- Matthew Rettig,
- Christopher K. Wong,
- Alana S. Weinstein,
- Vlado Uzunangelov,
- Josh M. Stuart,
- George V. Thomas,
- Felix Y. Feng,
- Eric J. Small,
- Joel A. Yates,
- Zheng Xia,
- Joshi J. Alumkal
Affiliations
- Thomas C. Westbrook
- Division of Hematology and Oncology, Department of Internal Medicine, Rogel Cancer Center, University of Michigan
- Xiangnan Guan
- Knight Cancer Institute, Oregon Health & Science University
- Eva Rodansky
- Division of Hematology and Oncology, Department of Internal Medicine, Rogel Cancer Center, University of Michigan
- Diana Flores
- Division of Hematology and Oncology, Department of Internal Medicine, Rogel Cancer Center, University of Michigan
- Chia Jen Liu
- Department of Pathology, Michigan Center for Translational Pathology, Rogel Cancer Center, University of Michigan
- Aaron M. Udager
- Department of Pathology, Michigan Center for Translational Pathology, Rogel Cancer Center, University of Michigan
- Radhika A. Patel
- Divisions of Human Biology and Clinical Research, Fred Hutchinson Cancer Research Center
- Michael C. Haffner
- Divisions of Human Biology and Clinical Research, Fred Hutchinson Cancer Research Center
- Ya-Mei Hu
- Knight Cancer Institute, Oregon Health & Science University
- Duanchen Sun
- Knight Cancer Institute, Oregon Health & Science University
- Tomasz M. Beer
- Knight Cancer Institute, Oregon Health & Science University
- Adam Foye
- Helen Diller Family Comprehensive Cancer Center, University of California San Francisco
- Rahul Aggarwal
- Helen Diller Family Comprehensive Cancer Center, University of California San Francisco
- David A. Quigley
- Helen Diller Family Comprehensive Cancer Center, University of California San Francisco
- Jack F. Youngren
- Helen Diller Family Comprehensive Cancer Center, University of California San Francisco
- Charles J. Ryan
- Masonic Cancer Center, University of Minnesota; Department of Laboratory Medicine and Pathology, University of Minnesota
- Martin Gleave
- Department of Urological Sciences and Vancouver Prostate Centre, University of British Columbia
- Yuzhuo Wang
- Department of Urological Sciences and Vancouver Prostate Centre, University of British Columbia
- Jiaoti Huang
- Duke University
- Ilsa Coleman
- Divisions of Human Biology and Clinical Research, Fred Hutchinson Cancer Research Center
- Colm Morrissey
- Department of Urology, University of Washington
- Peter S. Nelson
- Divisions of Human Biology and Clinical Research, Fred Hutchinson Cancer Research Center
- Christopher P. Evans
- University of California Davis
- Primo Lara
- University of California Davis
- Robert E. Reiter
- University of California Los Angeles
- Owen Witte
- Department of Microbiology, Immunology, and Molecular Genetics at the David Geffen School of Medicine, UCLA
- Matthew Rettig
- University of California Los Angeles
- Christopher K. Wong
- UC Santa Cruz Genomics Institute and Department of Biomolecular Engineering, University of California, Santa Cruz
- Alana S. Weinstein
- UC Santa Cruz Genomics Institute and Department of Biomolecular Engineering, University of California, Santa Cruz
- Vlado Uzunangelov
- UC Santa Cruz Genomics Institute and Department of Biomolecular Engineering, University of California, Santa Cruz
- Josh M. Stuart
- UC Santa Cruz Genomics Institute and Department of Biomolecular Engineering, University of California, Santa Cruz
- George V. Thomas
- Knight Cancer Institute, Oregon Health & Science University
- Felix Y. Feng
- Helen Diller Family Comprehensive Cancer Center, University of California San Francisco
- Eric J. Small
- Helen Diller Family Comprehensive Cancer Center, University of California San Francisco
- Joel A. Yates
- Division of Hematology and Oncology, Department of Internal Medicine, Rogel Cancer Center, University of Michigan
- Zheng Xia
- Knight Cancer Institute, Oregon Health & Science University
- Joshi J. Alumkal
- Division of Hematology and Oncology, Department of Internal Medicine, Rogel Cancer Center, University of Michigan
- DOI
- https://doi.org/10.1038/s41467-022-32701-6
- Journal volume & issue
-
Vol. 13,
no. 1
pp. 1 – 13
Abstract
Lineage plasticity is increasingly recognized as an emergent resistance mechanism after treatment with androgen receptor signalling inhibitors. To understand determinants of resistance, the authors analyzed the transcriptomes of patient tumor biopsies before enzalutamide treatment and at progression and identified a gene expression program associated with lineage plasticity risk and poor outcomes.