Clinical approaches to overcome PARP inhibitor resistance

PARP inhibitors have profoundly changed treatment options for cancers with homologous recombination repair defects, especially those carrying BRCA1/2 mutations. However, the development of resistance to these inhibitors presents a significant clinical challenge as it limits long-term effectiveness. This review provides an overview of the current understanding of resistance mechanisms to PARP inhibitors and explores strategies to overcome these challenges. We discuss the basis of synthetic lethality induced by PARP inhibitors and detail diverse resistance mechanisms affecting PARP inhibitors, including homologous recombination restoration, reduced PARP trapping, enhanced drug efflux, and replication fork…

• NN
  National Natural Science Foundation of China

  Awards: No. 82403976, 82403976
• NP
  National Postdoctoral Program for Innovative Talents

  Awards: BX20230447, No. BX20230447
• BA
  Basic and Applied Basic Research Foundation of Guangdong Province

  Awards: 2021B1515120053, 2025A1515012712, 2022B1515120087