Procyanidin C1 combined with olaparib induces senescence in BRCA1-proficient breast cancer cells.

PARP inhibitors (PARPi) are effective only in BRCA1-mutated tumors, with BRCA1-proficient patients deriving minimal benefit. Here, we demonstrate that PCC1 persistently induces double-strand DNA breaks (DSBs) in BRCA1-proficient breast cancer cells. Critically, PARP inhibition blocks base excision repair (BER), leading to accumulation of DNA damage and direct activation of senescence programs. Compared to monotherapy, the combination of olaparib and PCC1 significantly enhanced cellular senescence and suppressed tumor growth. In sum, we developed a novel therapeutic regimen that extends the utility of PARP inhibitors to BRCA1-proficient breast cancer patients through synergistic co-targeting of DNA damage responses.