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Review
. 2022 Dec;24(12):1685-1693.
doi: 10.1007/s11912-022-01337-6. Epub 2022 Nov 8.

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

Christina R Washington  1 , Kathleen N Moore  2
Affiliations
Review

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

Christina R Washington et al. Curr Oncol Rep. 2022 Dec.

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. 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.

Keywords: BRCA mutation; Epithelial ovarian cancer; Homologous recombination deficiency; Niraparib; Olaparib; PARP inhibitor resistance; PARP inhibitors; Restoration of homologous recombination proficiency; Rucaparib.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
    1. FDA label for Olaparib https://www.azpicentral.com/lynparza_tb/lynparza_tb.pdf#page=1last accessed February 15, 2022.
    1. FDA Approval for Rubraca: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/209115s003lbl.pdf Last Accessed February 15, 2022.
    1. Kaufman B, Shapira-Frommer R, Schmutzler RK, et al. Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutation. J Clin Oncol. 2015;33:244–50. - DOI - PubMed
    1. Swisher EM, Lin KK, Oza AM, et al. Rucaparib in relapsed, platinum-sensitive high-grade ovarian carcinoma (ARIEL2 Part 1): an international, multicentre, open-label, phase 2 trial. Lancet Oncol. 2017;18:75–87. - DOI - PubMed
    1. FDA label for niraparib: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/208447s015s017... . Last Accessed February 15, 2022.

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