ArticleAnnals of oncology : official journal of the European Society for Medical Oncology2018
The Warburg effect: persistence of stem-cell metabolism in cancers as a failure of differentiation.
Article in Annals of oncology : official journal of the European Society for Medical Oncology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
51 citing papers in PubMed, 1 synthesis or guideline pooled it, 81 citations in OpenAlex.
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- Intrinsic Tumor Aggressiveness Dictates Hypoxia-Driven Metabolic Programs in Hepatocellular Carcinoma.International journal of molecular sciences · 2026Article
- Can Serum Lactate on Admission to Intensive Care Predict Length of Stay? A Retrospective Analysis of Critically Ill Paediatric Oncology Patients.Journal of paediatrics and child health · 2025Observational
- Effects of circulating RNAs on tumor metabolism in lung cancer (Review).Oncology letters · 2025Review
- A Novel Ferroptosis-Related Gene Prognosis Signature and Identifying Atorvastatin as a Potential Therapeutic Agent for Hepatocellular Carcinoma.Current issues in molecular biology · 2025Article
- From Images to Genes: Radiogenomics Based on Artificial Intelligence to Achieve Non-Invasive Precision Medicine in Cancer Patients.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- NFκB and JNK pathways mediate metabolic adaptation upon ESCRT-I deficiency.Cellular and molecular life sciences : CMLS · 2024Article
- Targeting Lipid Metabolism in Cancer Stem Cells for Anticancer Treatment.International journal of molecular sciences · 2024Review
- Glucose metabolism transcriptome clustering identifies subsets of resectable lung adenocarcinoma with different prognoses.JTCVS open · 2024Article
- How General and Inflammatory Status Impacts on the Prognosis of Patients Affected by Lung Cancer: State of the Art.Biomedicines · 2024Review
- Multi-modality imaging parameters that predict rapid tumor regression in head and neck radiotherapy.Physics and imaging in radiation oncology · 2024Article
- TGF-β, IL-1β, IL-6 levels and TGF-β/Smad pathway reactivity regulate the link between allergic diseases, cancer risk, and metabolic dysregulations.Frontiers in immunology · 2024Article
- Lipid metabolism dynamics in cancer stem cells: potential targets for cancers.Frontiers in pharmacology · 2024Review
- Lipid metabolism-associated genes serve as potential predictive biomarkers in neoadjuvant chemoradiotherapy combined with immunotherapy in rectal cancer.Translational oncology · 2024Article
- The Emerging Roles of the Metabolic Regulator G6PD in Human Cancers.International journal of molecular sciences · 2023Review
- Epstein-Barr Virus Promotes Oral Squamous Cell Carcinoma Stemness through the Warburg Effect.International journal of molecular sciences · 2023Article
- Characterization of Mediastinal Bulky Lymphomas with FDG-PET-Based Radiomics and Machine Learning Techniques.Cancers · 2023Article
- Article
- Mitochondrial-Targeted Antioxidant MitoQ-Mediated Autophagy: A Novel Strategy for Precise Radiation Protection.Antioxidants (Basel, Switzerland) · 2023Article
- Cannot Target What Cannot Be Seen: Molecular Imaging of Cancer Stem Cells.International journal of molecular sciences · 2023Review
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
Abstract
Background: Two recent observations regarding the Warburg effect are that (i) the metabolism of stem cells is constitutive (aerobic) glycolysis while normal cellular differentiation involves a transition to oxidative phosphorylation and (ii) the degree of glucose uptake of a malignancy as imaged by 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is associated with histologic measures of tumor differentiation. Combining these observations, we hypothesized that the high levels of glucose uptake observed in poorly differentiated cancers may reflect persistence of the glycolytic metabolism of stem cells in malignant cells that fail to fully differentiate. Patients and methods: Tumor glucose uptake was measured by FDG-PET in 552 patients with histologically diverse cancers. We used normal mixture modeling to explore FDG-PET standardized uptake value (SUV) distributions and tested for associations between glucose uptake and histological differentiation, risk of lymph node metastasis, and survival. Using RNA-seq data, we carried out pathway and transcription factor analyses to compare tumors with high and low levels of glucose uptake. Results: We found that well-differentiated tumors had low FDG uptake, while moderately and poorly differentiated tumors had higher uptake. The distribution of SUV for each histology was bimodal, with a low peak around SUV 2-5 and a high peak at SUV 8-14. The cancers in the two modes were clinically distinct in terms of the risk of nodal metastases and death. Carbohydrate metabolism and the pentose-related pathway were elevated in the poorly differentiated/high SUV clusters. Embryonic stem cell-related signatures were activated in poorly differentiated/high SUV clusters. Conclusions: Our findings support the hypothesis that the biological basis for the Warburg effect is a persistence of stem cell metabolism (i.e. aerobic glycolysis) in cancers as a failure to transition from glycolysis-utilizing undifferentiated cells to oxidative phosphorylation-utilizing differentiated cells. We found that cancers cluster along the differentiation pathway into two groups, utilizing either glycolysis or oxidative phosphorylation. Our results have implications for multiple areas of clinical oncology.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.