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

Future Oncol. 2019 Oct;15(28):3283-3303. doi: 10.2217/fon-2019-0298. Epub 2019 Sep 19.

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.

Keywords: ATM; BRCA1; BRCA2; DDR; DNA damage response; genes; mutation; outcome; prostate cancer; therapy.

Publication types

  • Systematic Review

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • DNA Damage
  • DNA Repair
  • DNA Repair Enzymes / genetics*
  • Humans
  • Male
  • Mutation*
  • Prognosis
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / pathology

Substances

  • DNA Repair Enzymes