It appears that PARP-trapping compounds, as well as the potential future strategies/agents targeting XRCC1 and APE1, will be efficient primarily in preventing the acquisition of TMZ resistance via MMR deficiency but will not work on the primary MGMT-negative MMR-positive glioma since BER plays a minimal role in cell survival when the primary cytotoxic lesion is O6-meG. Here, PARP1 is linked to central nervous system cancer.