Abstract:Non-small cell lung cancer (NSCLC) is the main type of lung cancer, accounting for 85% to 90% of cases. The use of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) has greatly improved the prognosis of NSCLC patients. However, with prolonged drug use, the inevitable occurrence of acquired resistance leads to disease recurrence, progression, and even patients death. Metabolic reprogramming is one of the hallmarks of malignant tumors and refers to metabolic changes in tumor cells to meet energy needs. In various cancers, lipid synthesis, distribution, and catabolism of tumor cells are altered to adapt to the lack of nutrients and oxygen in the tumor microenvironment. This paper focuses on how lipid metabolism reprogramming in NSCLC leads to resistance to EGFR-TKIs and how modulation of lipid metabolism increases the sensitivity of NSCLC to EGFR-TKIs. It summarizes and consolidates existing research progress to provide a reference for basic research and clinical treatment of EGFR-TKIs resistance in NSCLC.