ArticleMolecular cancer therapeutics2013
Cetuximab reverses the Warburg effect by inhibiting HIF-1-regulated LDH-A.
Article in Molecular cancer therapeutics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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
55 citing papers in PubMed, 80 citations in OpenAlex.
- Multicenter open-label randomized phase II study of second-line panitumumab and irinotecan with or without fluoropyrimidines in patients with KRAS wild-type metastatic colorectal cancer (PACIFIC study).Medical oncology (Northwood, London, England) · 2019Trial
- The m6A/METTL3 modifies USP11 to promote Warburg effect progression of colon cancer undifferentiated by HIF-1α/YAP signaling pathway.Translational cancer research · 2026Article
- Hypoxia-inducible factors: Regulatory functions and status as a therapeutic target in gastric cancer (Review).Oncology letters · 2026Review
- Fraternal cooperation of hierarchical cancer parallels metazoan multicellularity and eusociality.Biological reviews of the Cambridge Philosophical Society · 2026Review
- ETS1 Promotes Aerobic Glycolysis and Growth in Head and Neck Squamous Cell Carcinoma by Targeting RRAS2.Biochemical genetics · 2025Article
- Metabolic imaging distinguishes ovarian cancer subtypes and detects their early and variable responses to treatment.Oncogene · 2025Article
- PPARα-mediated lipid metabolism reprogramming supports anti-EGFR therapy resistance in head and neck squamous cell carcinoma.Nature communications · 2025Article
- Impact of Nordihydroguaiaretic Acid on Proliferation, Energy Metabolism, and Chemosensitization in Non-Small-Cell Lung Cancer (NSCLC) Cell Lines.International journal of molecular sciences · 2024Article
- Connecting the dots: investigating the link between environmental, genetic, and epigenetic influences in metabolomic alterations in oral squamous cell carcinoma.Journal of experimental & clinical cancer research : CR · 2024Review
- Density Gradient Centrifugation Is an Effective Tool to Isolate Cancer Stem-like Cells from Hypoxic and Normoxia Triple-Negative Breast Cancer Models.International journal of molecular sciences · 2024Article
- Targeting the lactic acid metabolic pathway for antitumor therapy.Molecular therapy oncolytics · 2023Review
- Inhibition of Hypoxia-Inducible Transcription Factor (HIF-1α) Signaling with Sulfonyl-γ-AApeptide Helices.Journal of the American Chemical Society · 2023Article
- Mitochondrial metabolism: a predictive biomarker of radiotherapy efficacy and toxicity.Journal of cancer research and clinical oncology · 2023Review
- Review
- Sestrin2 in cancer: a foe or a friend?Biomarker research · 2022Review
- Targeting the Interplay between Cancer Metabolic Reprogramming and Cell Death Pathways as a Viable Therapeutic Path.Biomedicines · 2021Review
- Article
- Altered glycolysis results in drug-resistant in clinical tumor therapy.Oncology letters · 2021Review
- Glycolysis-induced drug resistance in tumors-A response to danger signals?Neoplasia (New York, N.Y.) · 2021Review
- The Mechanism of Warburg Effect-Induced Chemoresistance in Cancer.Frontiers in oncology · 2021Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Hypoxia-inducible factor-1 (HIF-1) plays a critical role in reprogramming cancer metabolism toward aerobic glycolysis (i.e., the Warburg effect), which is critical to supplying cancer cells with the biomass needed for proliferation. Previous studies have shown that cetuximab, an EGF receptor-blocking monoclonal antibody, downregulates the alpha subunit of HIF-1 (HIF-1α) through the inhibition of EGF receptor downstream cell signaling and that downregulation of HIF-1α is required for cetuximab-induced antiproliferative effects. However, the mechanism underlying these actions has yet to be identified. In this study, we used the Seahorse XF96 extracellular flux analyzer to assess the effect of cetuximab treatment on changes in glycolysis and mitochondrial respiration, the two major energy-producing pathways, in live cells. We found that cetuximab downregulated lactate dehydrogenase A (LDH-A) and inhibited glycolysis in cetuximab-sensitive head and neck squamous cell carcinoma (HNSCC) cells in an HIF-1α downregulation-dependent manner. HNSCC cells with acquired cetuximab resistance expressed a high level of HIF-1α and were highly glycolytic. Overexpression of a HIF-1α mutant (HIF-1α/ΔODD) conferred resistance to cetuximab-induced G1 phase cell-cycle arrest, which could be overcome by knockdown of LDH-A expression. Inhibition of LDH-A activity with oxamate enhanced the response of cetuximab-resistant cells to cetuximab. Cetuximab had no noticeable inhibitory effect on glycolysis in nontransformed cells. These findings provide novel mechanistic insights into cetuximab-induced cell-cycle arrest from the perspective of cancer metabolism and suggest novel strategies for enhancing cetuximab response.
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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.