[Glycolytic Reprogramming in Lung Adenocarcinoma:
Molecular Mechanisms, Metabolic Biomarkers and Targeted Therapeutic Strategies].

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, including 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 glycolytic reprogramming, aiming to provide insights for early screening, risk stratification, and metabolism-targeted therapies in LUAD.
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