Facing inevitable PARPis resistance: Mechanisms and therapeutic strategies for breast cancer treatment

Abstract

AbstractBRCA1/2 gene mutations, which result in a dysfunction of homologous recombination repair, have been discovered in at least 5% of breast cancer (BC) patients with the increase in BC incidence in recent years. PARP inhibitors (PARPis), the first drugs with clinical approval based on synthetic lethality, have been approved to treat BRCA1/2‐mutant BC. However, as with other targeted drugs, PARPis drug resistance has become a significant obstacle in the application of PARPis. In this paper, we discuss the mechanism of PARPis, the clinical application of PARPis as monotherapy and the possible induced resistance mechanism. By exploring the resistance mechanism, we aimed to identify appropriate effective therapeutic techniques to overcome PARPis resistance and improve the efficacy of PARPis as well as to provide theoretical and experimental evidence for the clinical use of PARPis in BRCA1/2‐mutant BC.