Although diverse cellular proteins including AMP-activated protein kinase, liver kinase B1 [36], OXPHOS complex 1 [37], and mitochondrial glycerolphosphate dehydrogenase [38] have been suggested as pharmacological targets of biguanides, we considered the NAD+/NADH imbalance caused by OXPHOS complex 1 inhibition a plausible mechanism by which phenformin acts on EGFR-TKI-resistant NSCLC. This evidence concerns the gene EGFR and non-small cell lung carcinoma.