[Homologous recombination deficiency and PARP inhibitors in therapeutics]

Bull Cancer. 2022 Jan;109(1):76-82. doi: 10.1016/j.bulcan.2021.09.015. Epub 2021 Nov 17.
[Article in French]

Abstract

PARP inhibitors are effective in different types of tumors such as ovarian, breast, prostate and pancreatic cancer. Many studies are in progress and may lead to prescription evolution. PARP inhibitors prescription is almost reserved to patients with a constitutional BRCA mutation or a somatic BRCA alteration or a tumor with a deficiency in homologous recombination. Nowadays, the diagnosis of homologous recombination deficit, HRD, is possible with the prescription of a myChoice CDx (Myriad) test. PARP inhibitors are studied in association with chemotherapy and targeted therapies but also with radiotherapy and with immune checkpoint inhibitors. Access to PARP inhibitors is challenged with the emergence of resistance mechanism. Various trials are now studying the possibility of reversing these resistance mechanisms.

Keywords: Déficit de la recombinaison homologue; Genomic signatures; Homologous recombination deficiency; Inhibiteurs de PARP; PARP inhibitor; Signatures génomiques.

Publication types

  • Review

MeSH terms

  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics
  • DNA Damage
  • DNA Repair-Deficiency Disorders / diagnosis*
  • Drug Resistance, Neoplasm* / genetics
  • Female
  • Genes, BRCA1
  • Genes, BRCA2
  • Homologous Recombination*
  • Humans
  • Indazoles / therapeutic use
  • Indoles / therapeutic use
  • Male
  • Ovarian Neoplasms / drug therapy
  • Ovarian Neoplasms / genetics
  • Pancreatic Neoplasms / drug therapy
  • Pancreatic Neoplasms / genetics
  • Phthalazines / therapeutic use
  • Piperazines / therapeutic use
  • Piperidines / therapeutic use
  • Poly(ADP-ribose) Polymerase Inhibitors / therapeutic use*
  • Prostatic Neoplasms / drug therapy
  • Prostatic Neoplasms / genetics
  • Recombinational DNA Repair

Substances

  • Indazoles
  • Indoles
  • Phthalazines
  • Piperazines
  • Piperidines
  • Poly(ADP-ribose) Polymerase Inhibitors
  • rucaparib
  • niraparib
  • olaparib