肺腺癌糖酵解重编程:分子机制、代谢标志物及靶向治疗策略OA

Lung adenocarcinoma(LUAD)is the most common and highly aggressive subtype of non-small cell lung cancer,characterized by metabolic reprogramming with enhanced glycolysis.Upregulation of key glycolytic enzymes[hexokinase 2(HK2),pyruvate kinase M2(PKM2),lactate dehydrogenase A(LDHA)]and lactate accumulation not only support tumor energy production and biosynthesis but also promote tumor progression and immune evasion through lactate-mediated immunosuppression and epigenetic regulation such as histone lactylation.Oncogenic signaling pathways,includ-ing phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/Akt/mTOR),hypoxia-inducible factor-1α(HIF-1α),and MYC proto-oncogene(c-Myc),synergistically drive glycolytic activation,thereby reshaping the tumor immune microenvironment and influencing therapeutic responses.In recent years,glycolysis-related metabolic enzymes and imaging parameters have shown promising potential in the early diagnosis,prognostic evaluation,and treatment monitoring of LUAD,with multi-omics integration further facilitating their clinical translation.Collectively,glycolytic reprogramming is not only a hallmark metabolic feature of LUAD but also a critical nexus linking immunosuppression,therapeutic resistance,and precision medicine.This review summarizes the molecular mechanisms,associated biomarkers,and targeted strategies of gly-colytic reprogramming,aiming to provide insights for early screening,risk stratification,and metabolism-targeted therapies in LUAD.