Because the metabolic shift to mitochondrial OXPHOS is triggered by long-term exposure to EGFR-TKIs, biguanide targeting OXPHOS may result in sustained redox stress as well as a subsequent aspartic acid deficiency and can be proposed as a new therapeutic option for NSCLC with acquired EGFR-TKI resistance. This evidence concerns the gene EGFR and non-small cell lung carcinoma.