Targeting glycolysis in non-small cell lung cancer: Promises and challenges
Open accessAbstract
Metabolic disturbance, particularly of glucose metabolism, is a hallmark of tumors such as non-small cell lung cancer (NSCLC). Cancer cells tend to reprogram a majority of glucose metabolism reactions into glycolysis, even in oxygen-rich environments. Although glycolysis is not an efficient means of ATP production compared to oxidative phosphorylation, the inhibition of tumor glycolysis directly impedes cell survival and growth. This review focuses on research advances in glycolysis in NSCLC and systematically provides an overview of the key enzymes, biomarkers, non-coding RNAs, and signaling pathways that modulate the glycolysis process and, consequently, tumor growth and metastasis in NSCLC. Current medications, therapeutic approaches, and natural products that affect glycolysis in NSCLC are also summarized. We found that the identification of appropriate targets and biomarkers in glycolysis, specifically for NSCLC treatment, is still a challenge at present. However, LDHB, PDK1, MCT2, GLUT1, and PFKM might be promising targets in the treatment of NSCLC or its specific subtypes, and DPPA4, NQO1, GAPDH/MT-CO1, PGC-1α, OTUB2, ISLR, Barx2, OTUB2, and RFP180 might be prognostic predictors of NSCLC. In addition, natural products may serve as promising therapeutic approaches targeting multiple steps in glycolysis metabolism, since natural products always present multi-target properties. The development of metabolic intervention that targets glycolysis, alone or in combination with current therapy, is a potential therapeutic approach in NSCLC treatment. The aim of this review is to describe research patterns and interests concerning the metabolic treatment of NSCLC.
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Most solid tumors, including LUAD, undergo a metabolic shift toward aerobic glycolysis (the Warburg effect) to satisfy the heightened energetic and biosynthetic demands imposed by rapid proliferation and a heterogeneous tumor microenvironment.
“Most solid tumors, including LUAD, undergo a metabolic shift toward aerobic glycolysis—notably the Warburg effect—to satisfy the heightened energetic and biosynthetic demands imposed by rapid proliferation and a heterogeneous tumor microenvironment (TME) (10).”
From Bioinformatics-based identification of glycolysis-related signatures associated with drug resistance and prognosis in lung adenocarcinoma (2026) · cites this paper as [10]
The Introduction (page unavailable) identifies aerobic glycolysis as the Warburg effect and says cancer cells reprogram metabolism to meet the demands of proliferation; it also reports enhanced aerobic glycolysis in NSCLC. The ‘Glycolytic metabolism in tumor cells’ section (page unavailable) links glycolysis to energy supply and materials for cell growth. The paper discusses interactions with the tumor microenvironment, but does not say that a heterogeneous microenvironment imposes the demands driving this shift; it also does not establish the claim specifically for LUAD. (LLM, conf=0.85)
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RETRACTED: Immunometabolism in lung cancer – The link between metabolism and immune response
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- Authors
- Xu, J.-Q., Fu, Y.-L., Zhang, J., Zhang, K.-Y., Ma, J., Tang, J.-Y., Zhang, Z.-W., & Zhou, Z.-Y.
- Affiliations
- Longhua Hospital Shanghai University of Traditional Chinese Medicine (CN)
- Corresponding author
- Zhou, Zhong-Yan
- Venue
- Frontiers in Pharmacology
- Publisher
- Frontiers Media SA
- Published
- 2022-11-30
- Volume
- 13
- Pages
- 1037341-1037341
- ISSN
- 1663-9812 (ISSN-L)
- PMC
- PMC9748442
- OpenAlex
- W4310995080
- Cited by
- 75
- References
- 151
- Citations by year
- 2026: 29 · 2025: 17 · 2024: 19 · 2023: 10
- FWCI
- 1.39
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Pharmacology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Shanghai Municipal Health Commission (22ZR1462200, GWIV-28, FWTX-8001)
- National Health Commission of the People's Republic of China
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Ferroptosis and cancer prognosis
- Keywords
- non-small cell lung cancer, glycolysis, tumor metabolic reprogramming, glucose metabolism, LDHB, PDK1, MCT2, GLUT1, PFKM, prognostic factors, non-coding RNA, signaling pathways, natural products, metabolic therapy, metastasis, therapeutic target
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