PARP-1 mutations could drive PARP inhibitor resistance

In a study published in Nature Communications, researchers from the Institute of Cancer Research (London, U.K.) suggested mutations in the PARP-1 gene may drive the resistance to PARP inhibitors seen in some cancer patients.

PARP-1 acts as a DNA damage sensor, binding DNA breaks as they occur and coordinating DNA damage repair. In tumor cells, small molecule PARP inhibitors such as Lynparza olaparib and talazoparib inhibit the ability of PARP-1 to help repair DNA defects, causing a buildup of mutations and subsequent cell death. Previous studies have suggested some PARP inhibitors may prevent DNA repair in tumors by immobilizing PARP-1 at sites of DNA damage, such that it cannot carry out its repair functions...