ATR and neoplasm: That inhibition of DNA-PKcs kinase activity can induce radiosensitization of tumor cells has been previously established genetically and pharmacologically (32, 35), and the ability of NU5455 to impart a greater radio-enhancement than small-molecule inhibitors of the DNA repair proteins ATM, PARP, and ATR is consistent with DNA-PK having a critical role in the repair of DNA-DSBs that represent the most lethal DNA damage lesion (1).