PARP inhibitors and breast cancer: from therapeutic breakthrough to resistance challenge

Abstract Breast cancer remains the leading cause of cancer-related mortality among women worldwide. Poly(ADP-ribose) polymerase (PARP) inhibitors have emerged as a critical therapeutic option, particularly for patients with triple-negative breast cancer and other HER2-negative metastatic breast cancer harboring BRCA mutations. Despite their clinical success, the emergence of primary and acquired resistance to PARP inhibitors poses a significant challenge, limiting their long-term effectiveness. Here we provide a comprehensive overview of the mechanisms underlying the action of PARP inhibitors, as well as their clinical development and application. In addition, we discuss the factors driving resistance and potential strategies to overcome it in the context of PARP inhibitors.