Mechanisms of PARP inhibitor resistance in cancer and insights into the DNA damage response

Genome Med. 2018 Dec 28;10(1):101. doi: 10.1186/s13073-018-0612-8.

Abstract

Inhibitors of poly(ADP-ribose) polymerase (PARPi) have entered the clinic for the treatment of patients with cancers that lack homology-directed DNA repair, but drug resistance remains a clinical hurdle. Recent advances in the identification of PARPi resistance mechanisms have yielded a better understanding of DNA end protection and the relevance of endogenous poly(ADP-ribose) glycohydrolase, highlighting new vulnerabilities.

Publication types

  • Letter
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • DNA Damage
  • DNA Repair*
  • DNA, Neoplasm / metabolism
  • Drug Resistance, Neoplasm*
  • Humans
  • Neoplasms / drug therapy*
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Poly(ADP-ribose) Polymerase Inhibitors / pharmacology*
  • Poly(ADP-ribose) Polymerase Inhibitors / therapeutic use

Substances

  • DNA, Neoplasm
  • Poly(ADP-ribose) Polymerase Inhibitors