Mechanisms of resistance to PARP inhibitors in ovarian cancer and strategies to overcome such resistance

doi:10.3877/cma.j.issn.1674-0785.2024.06.010

Abstract

Abstract:

The mortality of ovarian cancer ranks first among gynecological tumors, and defective DNA damage repair is one of the important causes of ovarian cancer. Frequent deletion mutations in breast cancer susceptibility genes (BRCA) 1 and 2 contribute to the impairment of homologous recombination repair (HRR) in ovarian cancer. Researchers have recently shown that the gene encoding poly(ADP-ribose) polymerase 1 (PARP1), a key enzyme for DNA repair, is synthetically lethal with BRCA1/2 double mutations. Therefore, PARP inhibitors (PARPi), such as olaparib, niraparib, and fluzoparib, have been approved as a new generation of targeted agents for ovarian cancer therapy. However, most patients with long-term PARPi therapy have varying degrees of drug resistance and even cross-resistance with cisplatin and other antitumor drugs. This article reviews the possible mechanisms of resistance to PARP inhibitors in ovarian cancer and corresponding coping strategies.

Key words: Ovarian cancer, Poly(ADP-ribose) polymerase 1, Poly(ADP-ribose) polymerase inhibitor, Resistance mechanism

Jingting Xu, Lu Kong. Mechanisms of resistance to PARP inhibitors in ovarian cancer and strategies to overcome such resistance[J]. Chinese Journal of Clinicians(Electronic Edition), 2024, 18(06): 584-588.

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References 43

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