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REVIEW article

Front. Oncol.
Sec. Gynecological Oncology
Volume 14 - 2024 | doi: 10.3389/fonc.2024.1414112
This article is part of the Research Topic PARP inhibitors resistance: new insights in ovarian cancer therapy View all 4 articles

Poly (ADP-ribose) polymerase (PARP) inhibitor therapy and mechanisms of resistance in epithelial ovarian cancer

Provisionally accepted
Sanat Kulkarni Sanat Kulkarni 1Ketankumar Gajjar Ketankumar Gajjar 2Srinivasan Madhusudan Srinivasan Madhusudan 3*
  • 1 Sandwell & West Birmingham Hospitals NHS Trust, West Bromwich, United Kingdom
  • 2 Other, Nottingham, United Kingdom
  • 3 University of Nottingham, Nottingham, United Kingdom

The final, formatted version of the article will be published soon.

    Advanced epithelial ovarian cancer is the commonest cause of gynaecological cancer deaths. First-line treatment for advanced disease includes a combination of platinumtaxane chemotherapy (post-operatively or peri-operatively) and maximal debulking surgery whenever feasible. Initial response rate to chemotherapy is high (up to 80%) but most patients will develop recurrence (approximately 70-90%) and succumb to the disease. Recently, poly-ADP-ribose polymerase (PARP) inhibition (by drugs such as Olaparib, Niraparib or Rucaparib) directed synthetic lethality approach in BRCA germline mutant or platinum sensitive disease has generated real hope for patients.PARP inhibitor (PARPi) maintenance therapy can prolong survival but therapeutic response is not sustained due to intrinsic or acquire secondary resistance to PARPi therapy. Reversion of BRCA1/2 mutation can lead to clinical PARPi resistance in BRCA-germline mutated ovarian cancer. However, in the more common platinum sensitive sporadic HGSOC, the clinical mechanisms of development of PARPi resistance remains to be defined. Here we provide a comprehensive review of the current status of PARPi and the mechanisms of resistance to therapy.

    Keywords: ovarian cancer, DNA Repair, PARP, PARP inhibitors, synthetic lethality, Resistance, DDR inhibitors

    Received: 08 Apr 2024; Accepted: 15 Jul 2024.

    Copyright: © 2024 Kulkarni, Gajjar and Madhusudan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Srinivasan Madhusudan, University of Nottingham, Nottingham, United Kingdom

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.