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

DOI
https://doi.org/10.1038/s41467-022-32701-6
Journal volume & issue
Vol. 13, no. 1
pp. 1 – 13

Abstract

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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.