EGFR and neoplasm: To address this knowledge gap, in the present study, we performed an isobolographic analysis to test the pharmacological interaction of metformin with either caffeine or DCA under normoxia and hypoxia conditions in the lung adenocarcinoma cell line HCC827 (CRL-2868), which has an Epidermal Growth Factor Receptor (EGFR) mutation and sensitivity to Tyrosine Kinase Inhibitors (TKIs), In addition, the lower oxygen consumption of this cell line facilitated the induction and controlled maintenance of hypoxia, allowing for a more accurate simulation of the tumor microenvironment.