In this study, we further showed that metformin synergizes the antiproliferation activity of EGFR TKI in TKI-resistance and/or CSE-treated NSCLC cells by enhancing AMPK-mediated reduction of mTOR/4EBP1 and ACC pathways (Fig. 5). Here, EIF4EBP1 is linked to non-small cell lung carcinoma.