Double-barreled gun: Combination of PARP inhibitor with conventional chemotherapy

Pharmacol Ther. 2018 Aug:188:168-175. doi: 10.1016/j.pharmthera.2018.03.006. Epub 2018 Apr 3.

Abstract

DNA repair pathways are evolutionarily conserved molecular mechanisms that maintain the integrity of genomic DNA. In cancer therapies, the integrity and activity of DNA repair pathways predict therapy resistance and disease outcome. Members of the poly (ADP-ribose) polymerase (PARP) family initiate and organize the biologic process of DNA repair, which counteracts many types of chemotherapies. Since the first development in approximately 3 decades ago, PARP inhibitors have greatly changed the concept of cancer therapy, leading to encouraging improvements in tumor suppression and disease outcomes. Here we summaries both pre-clinical and clinical findings of PARP inhibitors applications, particularly for combination therapies.

Keywords: Cancer; Chemoresistance; Chemotherapy; Combination therapy; DNA repair; PARP inhibitor.

Publication types

  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Animals
  • Combined Modality Therapy
  • DNA Repair / drug effects
  • Drug Resistance, Neoplasm
  • Humans
  • Neoplasms / drug therapy*
  • Poly(ADP-ribose) Polymerase Inhibitors / therapeutic use*
  • Temozolomide / therapeutic use

Substances

  • Poly(ADP-ribose) Polymerase Inhibitors
  • Temozolomide