Metabolic reprogramming underlying EGFR-TKI resistance in lung cancer.

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have significantly improved the clinical efficacy in non-small cell lung cancer (NSCLC) patients with EGFR mutations. However, acquired resistance to EGFR-TKIs remains an unavoidable therapeutic bottleneck. The metabolic reprogramming underlying this resistance is crucial for understanding the resistance mechanisms and identifying new therapeutic targets. Recently, an increasing number of studies have focused on the impact of metabolic reprogramming on acquired EGFR-TKI resistance. Collectively, this review reveals the core driving role of metabolic reprogramming in EGFR-TKI resistance, focuses on the systematic adjustments of resistant cells in terms of glucose metabolism, lipid metabolism, amino acid metabolism, and nucleotide metabolism, and also pays attention to the effects of ferroptosis and changes in the metabolic pattern of the tumor immune microenvironment on EGFR-TKI resistance. In addition, we summarize the application of potential therapeutic approaches targeting metabolic reprogramming in overcoming lung cancer resistance.