PARP inhibitor olaparib enhances the efficacy of radiotherapy on XRCC2-deficient colorectal cancer cells

• DOI: 10.1038/s41419-022-04967-7
• Publication Date: 2022-05-28T11:05:48Z
• Authors: Changjiang Qin; Zhiyu Ji; Ertao Zhai; Kaiwu Xu; Yijie Zhang; Quanying Li; Hong Jing; Xiaoliang Wang; Xinming Song
• Keywords: Olaparib; PARP inhibitor; PARP1; Radiosensitizer; Clonogenic assay; Synthetic Lethality

Abstract The use of PARP inhibitors in combination with radiotherapy is a promising strategy to locally enhance DNA damage tumors. Loss XRCC2 compromises repairs, and induced burdens may increase the reliance on PARP-dependent repairs cancer cells render cell susceptibility inhibitor therapy. Here we tested hypothesis that loss sensitizes colorectal (CRC) (RT). We show high levels or PARP1 LARC patients were significantly associated poor overall survival (OS). Co-expression analyses found low better OS. Our vitro experiments indicated olaparib+IR led reduced clonogenic survival, more damage, longer durations cycle arrest senescence XRCC2-deficient relative wild-type cells. Furthermore, our mouse xenograft RT + olaparib had greater anti-tumor effects long-term remission mice -deficient These findings suggest CRC acquires sensitivity inhibition after IR treatment supports clinical development for as radiosensitizer CRC.