Exercise-induced metabolic reprogramming in lung cancer and its translational implications for therapeutic advancement

Lung cancer remains one of the leading causes of cancer-related mortality worldwide, characterized by profound metabolic reprogramming that sustains malignant growth, immune evasion, and therapeutic resistance. Aberrant activation of glycolysis, increased fatty acid synthesis and uptake, and dysregulated glutamine metabolism provide energy and biosynthetic substrates while reshaping the tumor microenvironment through lactate accumulation, acidosis, and angiogenic signaling. Experimental and clinical evidence indicates that exercise may modulate aspects of these oncogenic metabolic pathways, enhance mitochondrial oxidative capacity, improve oxygen delivery, and restore systemic metabolic homeostasis. By modulating glycolytic flux, lipid turnover, and amino acid metabolism, exercise exerts comprehensive effects on both tumor cells and the host, alleviating cancer-associated cachexia, improving insulin sensitivity, and suppressing systemic inflammation. Exercise may also enhance immune competence and vascular function, thereby potentially promoting antitumor surveillance and supporting the therapeutic response.Integrated with conventional treatments such as chemotherapy, radiotherapy, and immunotherapy, exercise may serve as a non-pharmacological metabolic adjuvant that increases treatment tolerance, mitigates adverse effects, and improves quality of life. Furthermore, exercise-related metabolic, molecular, and physiological biomarkers, including glucose and lipid indices, insulin sensitivity parameters, irisin, cardiopulmonary performance indicators, and serum glycosylation profiles, offer promising tools for evaluating metabolic states and guiding personalized interventions. Collectively, these findings underscore exercise as a powerful modulator of tumor and host metabolism, aligning with the translational paradigm that bridges mechanistic discovery and clinical application. Future research should focus on defining standardized exercise prescriptions, validating predictive biomarkers, and elucidating subtype-specific responses to facilitate the integration of precision exercise therapy into lung cancer management.