Considering the role of IGFBP2 in forming the complex with EGFR and DNA-PKcs in DNA damage or drug resistance in EAC, the use of EGFR, DNA-PKcs inhibitors or the development of specific IGFBP2 inhibitors will be a promising therapeutic strategy as single agents or in combination with DNA damaging anti-cancer agents. The gene discussed is PRKDC; the disease is cancer.