Choosing wisely: Selecting PARP inhibitor combinations to promote anti-tumor immune responses beyond BRCA mutations

Gynecol Oncol. 2020 Feb;156(2):488-497. doi: 10.1016/j.ygyno.2019.09.021. Epub 2019 Oct 17.

Abstract

PARP inhibitors have transformed the management of advanced high-grade serous ovarian cancer. Despite the overwhelming success of PARP inhibition, particularly in BRCA-mutated ovarian cancer, several limitations and unanswered questions remain. With PARP inhibitors now being used in earlier treatment settings, the issue of both de novo and acquired resistance mechanisms and appropriate post-PARP management are pressing concerns. In addition, the population appropriate to target with PARP inhibitors and their use in patients without BRCA mutations is controversial and evolving. In this review we will discuss exciting PARP combinations and biologic rationale for the development and selection of PARP inhibitor combinations.

Keywords: DNA damage repair; Developmental therapeutics; Ovarian cancer; PARP inhibitors.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • BRCA1 Protein / genetics
  • BRCA2 Protein / genetics
  • DNA Repair
  • Female
  • Genes, BRCA1
  • Genes, BRCA2
  • Germ-Line Mutation
  • Humans
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / immunology*
  • Poly(ADP-ribose) Polymerase Inhibitors / administration & dosage*
  • Randomized Controlled Trials as Topic

Substances

  • BRCA1 Protein
  • BRCA1 protein, human
  • BRCA2 Protein
  • BRCA2 protein, human
  • Poly(ADP-ribose) Polymerase Inhibitors