Therapeutic advances and application of PARP inhibitors in breast cancer
Teng Zhou, Jian Zhang
Abstract
Targeting of DNA repair pathway is the main therapeutic approach for BRCA1 and BRCA2 associated tumors, including breast cancer. BRCA1/2 genes play a pivotal role in HRR pathway. Mutations in BRCA1/2 leads to DDR deficiency, which cause the increasing of genome instability, thus rendering cancer cells vulnerable to inhibition of DNA repair related proteins, such as PARP1. Pre-clinical studies has demonstrated that cancer cells with BRCA1/2 deficient are sensitive to PARPi, which are an emerging class of small molecule drug. Several clinical trials demonstrated the promising efficacy of PARP inhibitors for BRCA1/2 mutated breast cancer patient through selectively induce synthetic lethality cancer cells. Currently, four PARP inhibitors had been approved by FDA for clinical use. PARPi demonstrated to improve progression-free survival, while resistance to PARPi is inevitable. In this review article, we highlighted the advances in the PARPi clinical trials, resistance mechanism and coping strategies in breast cancer patients. We also summarized the international guideline and recommendations on PARP inhibitor usage in breast cancer.