PARP inhibitors for BRCA wild type ovarian cancer; gene alterations, homologous recombination deficiency and combination therapy

Jpn J Clin Oncol. 2019 Aug 1;49(8):703-707. doi: 10.1093/jjco/hyz090.

Abstract

After a brief summary of the current status of poly-ADP ribose polymerase (PARP) inhibitors for ovarian cancer, we summarize the current status of PARP inhibitors for BRCA wild type ovarian cancer, especially regarding gene alterations other than BRCA, homologous recombination deficiency (HRD), and combinations. Discussion of gene alterations other than BRCA include the results of multiple gene panels studying homologous recombination repair deficiency genes and cancer susceptibility genes, and influences of these alterations on efficacy of PARP inhibitors and cancer susceptibility. Discussions of HRD include the results of phase three trials using HRD assay, the definition of HRD assays, and the latest assays. Discussions of combinations include early phase trial results and ongoing trials combining PARP inhibitors with immune checkpoint inhibitors, anti-angiogenic agents, and triplets.

Keywords: BRCA wild type; HRD; LOH; PARP inhibitors; genetic counseling.

Publication types

  • Review

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • BRCA1 Protein / genetics*
  • BRCA2 Protein / genetics*
  • Female
  • Homologous Recombination / genetics*
  • Humans
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / genetics*
  • Poly(ADP-ribose) Polymerase Inhibitors / therapeutic use*

Substances

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