Genetic biomarkers to guide poly(ADP-ribose) polymerase inhibitor precision treatment of prostate cancer

Pharmacogenomics. 2020 Oct;21(15):1101-1115. doi: 10.2217/pgs-2020-0019. Epub 2020 Oct 6.

Abstract

Precision therapy for a subgroup of genetically defined metastatic castration-resistant prostate cancer patients may become a reality in the near future. DNA damage repair gene mutated prostate cancer might be vulnerable to treatment with PARP inhibitors (PARPi). PARPi clinical trials for prostate cancer investigate both germline and somatic genomic alterations of 43 genes for the applicability as genomic biomarker of PARPi sensitivity. Clinical trials with preliminary results show that BRCA2 and BRCA1, but also ATM, additionally BRIP1, FANCA, CDK12 and PALB2 may affect clinical end points, and may be potential candidates for genome-guided patient selection in PARPi treatment of prostate cancer.

Keywords: PARP inhibitors; castration-resistant prostate cancer; genomic biomarkers; precision treatment.

Publication types

  • Review

MeSH terms

  • Biomarkers, Tumor / genetics*
  • Clinical Trials as Topic / methods
  • Genetic Association Studies / methods
  • Genetic Markers / genetics*
  • Humans
  • Male
  • Poly(ADP-ribose) Polymerase Inhibitors / adverse effects
  • Poly(ADP-ribose) Polymerase Inhibitors / therapeutic use*
  • Precision Medicine / methods*
  • Prostatic Neoplasms, Castration-Resistant / drug therapy*
  • Prostatic Neoplasms, Castration-Resistant / genetics*

Substances

  • Biomarkers, Tumor
  • Genetic Markers
  • Poly(ADP-ribose) Polymerase Inhibitors