Although an activated glycolytic phenotype and non-mutational epigenetic reprogramming are emerging as important cancer hallmarks, their roles in third-generation EGFR-TKI resistance are not yet fully established.36,37 Our findings present the function of α-KG in linking BCAA metabolism to epigenetic regulation and glycolysis in TKI-resistant NSCLC, which provides an extensive understanding of the intricate crosstalk between multiple metabolic pathways and epigenetics in cancer development. This evidence concerns the gene EGFR and non-small cell lung carcinoma.