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Resistance to Poly (ADP-Ribose) Polymerase Inhibitors (PARPi): Mechanisms and Potential to Reverse

  • Gynecologic Cancers (NS Reed, Section Editor)
  • Published:
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Abstract

Purpose of Review

This review will focus on the most common mechanisms for poly (ADP-ribose) polymerase inhibitors’ (PARPi) resistance and the main strategies for overcoming acquired or de novo PARPi resistance.

Recent Findings

Initial approvals for PARPi as part of treatment for advanced epithelial ovarian cancer (EOC) started in 2014 with patient with recurrent cancer characterized by BRCA mutations in the 3rd and 4th line and now have approvals for front-line maintenance in both the BRCA mutated and BRCAwt populations.

Summary

As with all therapies, patients will eventually develop resistance to treatment. The most common mechanisms for PARPi resistance include reversion mutations, methylation events, and restoration of homologous recombination deficiency (HRD) through combinations and targeting replication stress. As more and more patients receive initial treatment (and potential retreatment with PARPi), we need to better understand the mechanisms in which tumors acquire PARPi resistance.

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Authors and Affiliations

  1. Stephenson Cancer Center, University of Oklahoma HSC, 800 NE 10th St, Suite 5050, Oklahoma City, OK, 73104, USA

    Christina R. Washington & Kathleen N. Moore

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Correspondence to Christina R. Washington.

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Conflict of Interest

Christina Washington declares no conflict of interest. Kathleen Moore declares personal fees and other from Astra Zeneca; grants, personal fees, and other from Genentech/Roche; grants, personal fees, and other from Immunogen; grants, personal fees, and other from GSK/Tesaro; other from Pfizer; personal fees from Aravive; personal fees from VBL Therapeutics; personal fees and other from Onco Med; grants and other from Lilly; personal fees from Eisai; personal fees from Vavotar; personal fees from Abbvie; personal fees from Tarveda; personal fees from Myriad; personal fees from Rubius; personal fees from Elevar; personal fees from Merck; personal fees from Mersana; personal fees from Sorrento; personal fees from OncXerna; personal fees from Alkemeres; personal fees from Blueprint Pharmaceuticals; personal fees from Mereo; and personal fees from IMab, outside the submitted work, and serves as the Associate Director for GOG Partners and is a GOG Foundation Board of Directors member.

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Washington, C.R., Moore, K.N. Resistance to Poly (ADP-Ribose) Polymerase Inhibitors (PARPi): Mechanisms and Potential to Reverse. Curr Oncol Rep 24, 1685–1693 (2022). https://doi.org/10.1007/s11912-022-01337-6

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