Consistent with these results, we underscore a particularly important function in which FEN1 serves as a synthetic lethal target in DNA-PKcs-deficient glioma cells and demonstrate novel links between FEN1, BRCA1/2, RAD51, and WRN gene regulatory function and the signaling mechanism of DNA-PKcs-independent glioma cells survival and tumor growth. The gene discussed is PRKDC; the disease is central nervous system cancer.