ArticleCancer prevention research (Philadelphia, Pa.)2015
Prevention of tumor growth driven by PIK3CA and HPV oncogenes by targeting mTOR signaling with metformin in oral squamous carcinomas expressing OCT3.
Article in Cancer prevention research (Philadelphia, Pa.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
48 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.
- Effects of metformin on head and neck cancer: an umbrella review.BMC cancer · 2026Pooled it
- Inhibition of mTOR signaling and clinical activity of metformin in oral premalignant lesions.JCI insight · 2021Trial
- Protein expression of ABCC2 and SLC22A3 associates with prognosis of pancreatic adenocarcinoma.Scientific reports · 2019Trial
- Met Receptor Tyrosine Kinase and Chemoprevention of Oral Cancer.Journal of the National Cancer Institute · 2018Trial
- Comparison of Metformin Combinations with Other Repurposed Drugs in the Treatment of Hamster Fibrosarcoma: A Review.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Tissue Context Shapes Distinct Premalignant Outcomes in an HPV16 E6/E7-Mutant Pik3ca Transgenic Mouse Model.Cancer research communications · 2026Article
- Targeting metabolic reprogramming in HPV-associated oral squamous cell carcinoma: current advances, challenges, and clinical prospects.Journal of molecular histology · 2026Review
- Loss of Gαq reshapes fibroblast traits and drives tumor-stroma remodeling in oral cancer progression.EMBO reports · 2026Article
- Genome-wide CRISPR Screening Reveals a PKA-Driven Resistance Mechanism to Metformin for Oral Cancer Prevention That Can Be Exploited by Combination with NSAIDs.Cancer prevention research (Philadelphia, Pa.) · 2026Article
- Signaling pathways and targeted interventions for precancers.Signal transduction and targeted therapy · 2026Review
- Cardioprotective Effect of Metformin Treatment in Mouse Model of Experimental Autoimmune Myocarditis.Cardiovascular therapeutics · 2026Article
- The significance of mitochondrial DNA changes during the onset and progression of head and neck squamous cell carcinoma.Future oncology (London, England) · 2026Review
- Interconnected Mechanistic Pathways, Molecular Biomarkers, and Therapeutic Approach of Oral Cancer in Patients with Diabetes Mellitus.Current issues in molecular biology · 2025Review
- Biological Anti-Tumoral Mechanisms of Metformin in Head and Neck Squamous Cell Carcinomas: A Systematic Review.Journal of clinical medicine · 2025Review
- High fructose consumption aggravates inflammation by promoting effector T cell generation via inducing metabolic reprogramming.Signal transduction and targeted therapy · 2025Article
- Oncogenic HRAS Induces Metformin Resistance in Head and Neck Cancer by Promoting Glycolytic Metabolism.Cancer prevention research (Philadelphia, Pa.) · 2024Article
- Article
- Molecular and cellular mechanisms underlying the failure of mitochondrial metabolism drugs in cancer clinical trials.The Journal of clinical investigation · 2024Article
- The mechanisms of action of metformin on head and neck cancer in the pre-clinical setting: a scoping review.Frontiers in oncology · 2024Article
- Exploring animal models in oral cancer research and clinical intervention: A critical review.Veterinary medicine and science · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 7 institutions in 2 countries.
Funding
Abstract
Most squamous cell carcinomas of the head and neck (HNSCC) exhibit a persistent activation of the PI3K-mTOR signaling pathway. We have recently shown that metformin, an oral antidiabetic drug that is also used to treat lipodystrophy in HIV-infected (HIV(+)) individuals, diminishes mTOR activity and prevents the progression of chemically induced experimental HNSCC premalignant lesions. Here, we explored the preclinical activity of metformin in HNSCCs harboring PIK3CA mutations and HPV oncogenes, both representing frequent HNSCC alterations, aimed at developing effective targeted preventive strategies. The biochemical and biologic effects of metformin were evaluated in representative HNSCC cells expressing mutated PIK3CA or HPV oncogenes (HPV(+)). The oral delivery of metformin was optimized to achieve clinical relevant blood levels. Molecular determinants of metformin sensitivity were also investigated, and their expression levels were examined in a large collection of HNSCC cases. We found that metformin inhibits mTOR signaling and tumor growth in HNSCC cells expressing mutated PIK3CA and HPV oncogenes, and that these activities require the expression of organic cation transporter 3 (OCT3/SLC22A3), a metformin uptake transporter. Coexpression of OCT3 and the mTOR pathway activation marker pS6 were observed in most HNSCC cases, including those arising in HIV(+) patients. Activation of the PI3K-mTOR pathway is a widespread event in HNSCC, including HPV(-) and HPV(+) lesions arising in HIV(+) patients, all of which coexpress OCT3. These observations may provide a rationale for the clinical evaluation of metformin to halt HNSCC development from precancerous lesions, including in HIV(+) individuals at risk of developing HPV(-) associated cancers.
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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.