Chromatin to Clinic: The Molecular Rationale for PARP1 Inhibitor Function

Mol Cell. 2015 Jun 18;58(6):925-34. doi: 10.1016/j.molcel.2015.04.016.

Abstract

Poly(ADP-ribose) polymerase 1 (PARP1) inhibitors were recently shown to have potential clinical impact in a number of disease settings, particularly as related to cancer therapy, treatment for cardiovascular dysfunction, and suppression of inflammation. The molecular basis for PARP1 inhibitor function is complex, and appears to depend on the dual roles of PARP1 in DNA damage repair and transcriptional regulation. Here, the mechanisms by which PARP-1 inhibitors elicit clinical response are discussed, and strategies for translating the preclinical elucidation of PARP-1 function into advances in disease management are reviewed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromatin / genetics*
  • DNA Repair*
  • Enzyme Inhibitors / therapeutic use
  • Humans
  • Molecular Targeted Therapy / methods
  • Molecular Targeted Therapy / trends
  • Neoplasms / drug therapy
  • Neoplasms / genetics
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Poly(ADP-ribose) Polymerases / metabolism*
  • Transcription, Genetic*
  • Translational Medical Research / methods
  • Translational Medical Research / trends

Substances

  • Chromatin
  • Enzyme Inhibitors
  • Poly(ADP-ribose) Polymerase Inhibitors
  • PARP1 protein, human
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases