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STAT1 dependent interferon-related DNA damage resistance signature (IRDS) is a survival mechanism in castrate resistant prostate cancer (CRPC)

Friday, September 15, 2017 — Poster Session IV

1:00 p.m. – 2:30 p.m.
FAES Terrace
NCI
CANCER-9

Authors

  • S AGARWAL
  • K McGowen
  • K Kelly

Abstract

Contrary to the anti-proliferative interferon (IFN) signaling, IFN related DNA damage resistance signature (IRDS) has pro-survival function and is responsible for cancer cell intrinsic therapy resistance. This signature encompasses a subset of STAT1-driven genes that have been associated with breast cancer therapy resistance. Interestingly, our RNAseq analysis of organoids from FACS-sorted Pten/Tp53-null PCa luminal progenitors have revealed a robust IRDS expression. Based on our previous findings that the luminal progenitors display intrinsic resistance to androgen deprivation therapy (ADT), we hypothesized that the IRDS expression might in part account for survival of PCa cells following ADT or genotoxic therapies. Our analysis of human PCa datasets revealed IRDS as a prognostic marker for progression in the TCGA primary PCa cohort (p

Category: Cancer Biology