PARP inhibitor + checkpoint inhibitor

The combination of a PARP (poly ADP-ribose polymerase) inhibitor and an immune checkpoint inhibitor is an investigational therapeutic strategy for cancer. PARP inhibitors, such as olaparib, niraparib, rucaparib, and talazoparib, block the repair of DNA damage in tumor cells—especially those with homologous recombination deficiencies (HRD), including BRCA1/2 mutations—leading to synthetic lethality. Immune checkpoint inhibitors (ICIs), such as anti-PD-1/PD-L1 or anti-CTLA-4 antibodies (e.g., pembrolizumab, nivolumab), enhance antitumor immunity by blocking inhibitory pathways that restrain T cell activity. Mechanistically, PARP inhibition increases genomic instability and upregulates PD-L1 expression on tumor cells via activation of the cGAS-STING pathway. This leads to increased neoantigen formation and recruitment of dendritic cells and T lymphocytes into the tumor microenvironment. The resulting immunogenicity may sensitize tumors to ICIs. Clinical trials have shown that this combination can produce durable responses in patients with advanced solid tumors harboring HRR gene mutations or HRD positivity—including breast, ovarian, prostate cancers—and is being explored across multiple cancer types[1][2][3][5].

Other names

PARPi + ICIPARP inhibitor and immune checkpoint inhibitor combinationPARP inhibitor plus checkpoint blockade