Poly(ADP-ribose) polymerase activity and inhibition in cancer

Caleb Dulaney, Samuel Marcrom, Jennifer Stanley, Eddy S. Yang

Research output: Contribution to journalReview articlepeer-review

54 Scopus citations

Abstract

Genomic instability resultant from defective DNA repair mechanisms is a fundamental hallmark of cancer. The poly(ADP-ribose) polymerase (PARP) proteins 1, 2 and 3 catalyze the polymerization of poly(ADP-ribose) and covalent attachment to proteins in a phylogenetically ancient form of protein modification. PARPs play a role in base excision repair, homologous recombination, and non-homologous end joining. The discovery that loss of PARP activity had cytotoxic effects in cells deficient in homologous recombination has sparked a decade of translational research efforts that culminated in the FDA approval of an oral PARP inhibitor for clinical use in patients with ovarian cancer and defective homologous recombination. Five PARP inhibitors are now in late-stage development in clinical trials that are seeking to expand the understanding of targeted therapies and DNA repair defects in human cancer. This review examines the cell biology of PARP, the discovery of synthetic lethality with HR deficiency, the clinical development of PARP inhibitors, and the role of PARP inhibitors in ongoing clinical trials and clinical practice.

Original languageEnglish
Pages (from-to)144-153
Number of pages10
JournalSeminars in Cell and Developmental Biology
Volume63
DOIs
StatePublished - Mar 1 2017

Bibliographical note

Publisher Copyright:
© 2017 Elsevier Ltd

Keywords

  • DNA repair
  • PARP
  • PARP inhibitors
  • Poly(ADP-ribose) polymerase
  • Synthetic lethality

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology

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