You are here

Article Text

Article menu
Download PDFPDF
Review
Overcoming PARP inhibitor resistance in ovarian cancer
  1. Pamela Soberanis Pina and
  2. Stephanie Lheureux
  1. Medical Oncology, Princess Margaret Hospital Cancer Centre, Toronto, Ontario, Canada
  1. Correspondence to Dr Stephanie Lheureux, Princess Margaret Hospital Cancer Centre, Toronto, Canada; Stephanie.Lheureux{at}uhn.ca

Abstract

Ovarian cancer (OC) is one of the most lethal tumors in women, mostly diagnosed at advanced stages. Standard of care is based on surgery and platinum-based chemotherapy which provides high rates of response, although most patients will relapse. Poly(ADP-ribose) polymerase inhibitors (PARPi) have recently been incorporated in the treatment strategy for high-grade OC, particularly for those with defects in DNA repair pathways (homologous repair deficiency (HRd)). However, some tumor cells may not respond and some others will develop mechanisms of resistance to adapt. The most known mechanism of PARPi resistance is the reversion of HRd to homologous repair proficiency driven by epigenetic and genetic changes. Ongoing research is exploring different agents that are trying to re-sensitize tumor cells,overcome or bypass resistance to PARPi. Current investigations are focused on agents that target replication stress and DNA repair pathways, improve drug delivery, and target other cross-talk pathways. A crucial challenge in practice will be to identify and select patients for the appropriate therapy or combination strategies. However, efforts are needed to decrease overlapping toxicity and define the correct schedule timing of dosing to maximize the therapeutic index.

  • ovarian cancer
  • homologous recombination

https://doi.org/10.1136/ijgc-2022-003698

Statistics from Altmetric.com

    Request Permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

    View Full Text

    Footnotes

    • Twitter @stephanielheur5

    • Contributors Conception and design: SL. Manuscript writing: All authors. Editing: All authors. Final approval of manuscript: SL.

    • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

    • Competing interests SL reports grants or contracts to their institution from Merck, AstraZeneca, Regeneron, Roche, Repare, GSK, Seagen; consulting fees from Novocure, Merck, AstraZeneca, GSK, Roche, Eisai, and Shattuck Labs; payment or honoraria for lectures, presentations, speakers bureaus, or educational events from AstraZeneca, GSK, and Eisai; and participation on a data safety monitoring board or advisory board from AstraZeneca. She has been principal investigator or co-investigator of different trials with PARPi and DDR agents. PSP declares no potential conflicts of interest.

    • Provenance and peer review Commissioned; internally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.