Role of metabolic reprogramming in drug resistance to epidermal growth factor tyrosine kinase inhibitors in non-small cell lung cancer.

Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) can effectively inhibit the growth of EGFR-dependent mutant non-small cell lung cancer (NSCLC). Unfortunately, NSCLC patients often develop severe drug resistance after long-term EGFR-TKI treatment. Studies have shown that the disorder of energy metabolism in tumor cells can induce EGFR-TKI resistance. Due to the drug action, gene mutation and other factors, tumor cells undergo metabolic reprogramming, which increases the metabolic rate and intensity of tumor cells, promotes the intake and synthesis of nutrients (such as sugar, fat and glutamine), forms a microenvironment conducive to tumor growth, enhances the bypass activation, phenotype transformation and abnormal proliferation of tumor cells, and inhibits the activity of immune cells and apoptosis of tumor cells, ultimately leading to drug resistance of tumor cells to EGFR-TKI. Therefore, targeting energy metabolism of NSCLC may be a potential way to alleviate TKI resistance.