Combined TP53 and RB1 Loss Promotes Prostate Cancer Resistance to a Spectrum of Therapeutics and Confers Vulnerability to Replication Stress

Michael D. Nyquist, Alexandra Corella, Ilsa Coleman, Navonil De Sarkar, Arja Kaipainen, Gavin Ha, Roman Gulati, Lisa Ang, Payel Chatterjee, Jared Lucas, Colin Pritchard, Gail Risbridger, John Isaacs, Bruce Montgomery, Colm Morrissey, Eva Corey, Peter S. Nelson

Research output: Contribution to journalArticleResearchpeer-review

26 Citations (Scopus)

Abstract

Nyquist et al. demonstrate that TP53 and RB1 loss in prostate carcinoma (PC) attenuates AR signaling and enhances cell proliferation but does not uniformly induce neuroendocrine phenotypes. PCs with TP53/RB1 loss resist a wide range of cancer therapeutics but respond to PARP and ATR inhibition, likely reflecting enhanced replication stress.

Original languageEnglish
Article number107669
Number of pages23
JournalCell Reports
Volume31
Issue number8
DOIs
Publication statusPublished - 26 May 2020

Keywords

  • androgen receptor
  • antiandrogen
  • ATR
  • DNA damage
  • neuroendocrine
  • PARP
  • plasticity
  • prostate cancer
  • RB1
  • TP53

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