Mechanisms of Resistance to PARP Inhibitor and Strategies to Improve Its Sensitivity in Epithelial Ovarian Cancer

doi:10.12280/gjfckx.20230839

Abstract

Abstract:

The fatality rate of epithelial ovarian cancer (EOC) ranks first among malignant tumors of the female reproductive system. The traditional treatment approach for EOC involves cytoreductive surgery combined with platinum-based chemotherapy. However, within 2 years, approximately 70% of patients experience relapse or develop resistance. Poly (ADP-ribose) polymerase (PARP) inhibitors, as a novel molecular targeted drug, exert the "synthetic-lethal" effect on tumor cells with breast cancer-related gene (BRCA) mutations, offering a brand-new therapeutic model for EOC. PARP inhibitors have brought significant breakthroughs in targeted maintenance therapy for EOC. However, some patients still gradually fail to respond to PARP inhibitors, and the main resistance mechanisms include homologous recombination repair (HRR) recovery, drug target changes, and reduction of fatal DNA damage. Current strategies to improve its sensitivity include combining with DNA damage repair inhibitors, drugs that inhibit the HRR pathway, traditional anticancer regimens, P-glucoprotein (P-gp) inhibitors, and replacing alternative types of PARP inhibitors.

Key words: Poly(ADP-ribose) polymerase inhibitors, Ovarian neoplasms, Neoplasms, glandular and epithelial, Homologous recombination, Genes, BRCA1, Genes, BRCA2, Drug therapy

ZHANG Wen-yang, WANG Xi-peng. Mechanisms of Resistance to PARP Inhibitor and Strategies to Improve Its Sensitivity in Epithelial Ovarian Cancer[J]. Journal of International Obstetrics and Gynecology, 2024, 51(1): 52-59.

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