DNA-PKcs is the core enzyme for repair of DSBs through NHEJ and is involved in multiple tumor-associated pathways.18 DNA-PKcs-deficient cells are hypersensitive to IR.23 We previously reported that overexpression of mutated K-RAS(V12) in K-RAS wild-type cells results in enhanced radiation-induced DNA-PKcs dependent repair activity, which leads to cellular radioresistance.17 We now demonstrate that targeting the DNA-PKcs kinase activity reverses radioresistance of K-RAS-mutated A549 cells. The gene discussed is PRKDC; the disease is neoplasm.