Effect of DNA damage response mutations on prostate cancer prognosis: a systematic review

Stephanie L. Swift*, Shona H. Lang, Heath White, Kate Misso, Jos Kleijnen, Ruben G. W. Quek

*Corresponding author for this work

Research output: Contribution to journal(Systematic) Review article peer-review

Abstract

The prognosis of men with prostate cancer (PC) with mutations in DNA damage response (DDR) genes undergoing different treatments is unclear. This systematic review compared clinical outcomes in PC patients with DDR mutations (DDR+) versus no mutations (DDR-). 14 resources plus gray literature were searched for studies in PC and subgroups (castration-resistant PC, metastatic PC and metastatic castration-resistant PC) by DDR gene (ATM, ATR, BRCA1, BRCA2, CHEK2, FANCA, MLH1, MRE11A, NBN, PALB2, RAD51C) mutation status. From 11,648 records, 26 studies were included. For mCRPC, six studies reported comparative efficacy for key outcomes. Improvements in several clinical outcomes were observed for DDR+ (vs DDR-) after PARP inhibitor therapy or immunotherapy. DDR+ PC patients may have improved outcomes depending on the treatment they undergo.

Original languageEnglish
Pages (from-to)3283-3303
Number of pages20
JournalFuture Oncology
Volume15
Issue number28
DOIs
Publication statusPublished - Oct 2019

Keywords

  • ATM
  • BRCA1
  • BRCA2
  • DDR
  • DNA damage response
  • genes
  • mutation
  • outcome
  • prostate cancer
  • therapy
  • BRCA MUTATIONS
  • REPAIR
  • RADIATION
  • ASSOCIATION
  • VARIANTS
  • TOXICITY
  • THERAPY
  • RISK
  • MEN
  • POLYMORPHISMS

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