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Peer-reviewedCC BY-NC-ND 4.0Journal of Translational Medicine

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

  • Yonghua Zheng1,2
  • Yisheng Chen3,4,5,6,7
  • Hanyang Zhao7
  • Guanghui Wu3,4,5,6,7
  • Chen Hua8
  • Fu Gao9
  • Yue Liu10
  • Lei Jiang11
  • Lihua Dai12,13
13 affiliations
  1. 1Respiratory and Intensive Care Unit, Shidong Hospital Affiliated to University of Shanghai for Science and Technology, Shanghai, China
  2. 2Respiratory and Intensive Care Unit, Shidong Hospital of Yangpu District, Shanghai, China
  3. 3Fujian Key Laboratory of Toxicant and Drug Toxicology, Medical College, Ningde Normal University, Ningde, China
  4. 4Ningde Normal University, Ningde, China
  5. 5Department of Vascular and Interventional Radiology, Ningde Municipal Hospital of Ningde Normal University, Ningde, China
  6. 6Fujian Key Laboratory of Medical Bioinformatics, Fujian Medical University, Fuzhou, China
  7. 7Ningde Clinical Medical College of Fujian Medical University, Ningde, China
  8. 8Universiti Malaya, Kuala Lumpur, Malaysia
  9. 9Yale School of Medicine, New Haven, CT USA
  10. 10Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, USA
  11. 11Thoracic Department, Tongji University Affiliated Shanghai Pulmonary Hospital, Shanghai, China
  12. 12Emergency and Intensive Care Unit, Shidong Hospital Affiliated to University of Shanghai for Science and Technology, Shanghai, China
  13. 13Emergency and Intensive Care Unit, Shidong Hospital of Yangpu District, Shanghai, China
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Abstract

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.

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Cite

BibTeXRIS
BibTeX
@article{zheng2026exerciseinduced,
  title = {{Exercise-induced metabolic reprogramming in lung cancer and its translational implications for therapeutic advancement}},
  author = {Yonghua Zheng and Yisheng Chen and Hanyang Zhao and Guanghui Wu and Chen Hua and Fu Gao and Yue Liu and Lei Jiang and Lihua Dai},
  journal = {Journal of Translational Medicine},
  year = {2026},
  month = aug,
  doi = {10.1186/s12967-026-08665-2},
  url = {https://doi.org/10.1186/s12967-026-08665-2},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - Exercise-induced metabolic reprogramming in lung cancer and its translational implications for therapeutic advancement
AU  - Yonghua Zheng
AU  - Yisheng Chen
AU  - Hanyang Zhao
AU  - Guanghui Wu
AU  - Chen Hua
AU  - Fu Gao
AU  - Yue Liu
AU  - Lei Jiang
AU  - Lihua Dai
PY  - 2026
DA  - 2026/08/06
JO  - Journal of Translational Medicine
DO  - 10.1186/s12967-026-08665-2
UR  - https://doi.org/10.1186/s12967-026-08665-2
AB  - 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.
SN  - 1479-5876
ER  -