PARP inhibitor-based combination therapies: Enriching synergistic forces against BRCA-mutated metastatic breast cancer.

Metastatic breast cancer (MBC) harboring BRCA mutation is typically characterized by impaired DNA damage repair, namely homologous recombination deficiency (HRD). Targeting HRD via synthetic lethality, evolving poly(ADP-ribose) polymerase inhibitors (PARPi) have revolutionized the therapeutic paradigm of BRCA-mutated MBC. Numerous researches have indicated that PARPi monotherapy could exhibit certain anti-tumor efficacy. However, it was also verified that PARPi, when applied alone, was associated with disfavored toxicity and tendency to drug resistance. Therefore, the indication of single PARPi in MBC remained narrow, which remarkably limited their clinical application. Nowadays, PARPi-based combination therapies have appealed to incremental attentions, bringing about a series of promising opportunities and noteworthy challenges. In this review, we update both preclinical and clinical advances about multiple PARPi-based synergistic tactics against BRCA-mutated MBC, aiming to identify potential prognostic factors and biomarkers, as well as pave the way for further enrichment of treatment options for MBC patients carrying BRCA mutations.