Trial reportJCI insight2021
Inhibition of mTOR signaling and clinical activity of metformin in oral premalignant lesions.
Trial report in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
41 citing papers in PubMed, 65 citations in OpenAlex.
- Blueberry Extract Has Anti-Proliferative Activity in Preclinical Models of Head and Neck Cancer.Head & neck · 2026Article
- Effects of anti-diabetic medications on the teeth, oral soft and hard tissues, saliva, and implants: a scoping review.BDJ open · 2026Review
- From Chronic Inflammation to Malignancy: Molecular Mechanisms and Therapeutic Insights in Oral Carcinogenesis.International journal of molecular sciences · 2026Review
- Fanconi Anemia as a Window into Premalignant Field Cancerization of the Oral Mucosa.medRxiv : the preprint server for health sciences · 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
- Mechanistic Links Between the Gut Microbiome and Longevity Therapeutics.Biomedicines · 2026Review
- Signaling pathways and targeted interventions for precancers.Signal transduction and targeted therapy · 2026Review
- Metformin alleviates the progression of oral submucous fibrosis through downregulation of metastasis associated lung adenocarcinoma transcript 1 (MALAT1).Journal of dental sciences · 2026Article
- Mitochondrial-targeted therapeutics in oral squamous cell carcinoma: molecular and therapeutic implications.Frontiers in medicine · 2026Review
- Integration of artificial intelligence and high-content screening enabled identification of drugs for long-term treatment of cerebral cavernous malformation disease.bioRxiv : the preprint server for biology · 2025Article
- Interconnected Mechanistic Pathways, Molecular Biomarkers, and Therapeutic Approach of Oral Cancer in Patients with Diabetes Mellitus.Current issues in molecular biology · 2025Review
- Curcumin suppresses colorectal cancer by inhibiting TRIM2 and mTOR signaling.Translational oncology · 2025Article
- Effect of metformin on hypoxia-associated gene expression in oral cavity squamous cell carcinoma in non-diabetic patients - a prospective window of opportunity study.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2025Article
- Prevalence and Risk Factors of Oral Lesions in a Portuguese Subpopulation: A Retrospective Study.Journal of clinical medicine · 2025Article
- Clinical Management Update of Oral Leukoplakia: A Review From the American Head and Neck Society Cancer Prevention Service.Head & neck · 2025Review
- Targeting AMPK for Cancer Therapy: Metabolic Reprogramming as a Therapeutic Strategy.Oncology research · 2025Review
- Metabolomic Profiling of Oral Potentially Malignant Disorders and Its Clinical Values.Biomedicines · 2024Review
- Oncogenic HRAS Induces Metformin Resistance in Head and Neck Cancer by Promoting Glycolytic Metabolism.Cancer prevention research (Philadelphia, Pa.) · 2024Article
- Chemoprevention of Head and Neck Cancer: A Review of Current Approaches and Future Perspectives.Cancer prevention research (Philadelphia, Pa.) · 2024Review
- A Narrative Review: Repurposing Metformin as a Potential Therapeutic Agent for Oral Cancer.Cancers · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
22 authors at 5 institutions in 2 countries.
Funding
Abstract
BACKGROUNDThe aberrant activation of the PI3K/mTOR signaling circuitry is one of the most frequently dysregulated signaling events in head and neck squamous cell carcinoma (HNSCC). Here, we conducted a single-arm, open-label phase IIa clinical trial in individuals with oral premalignant lesions (OPLs) to explore the potential of metformin to target PI3K/mTOR signaling for HNSCC prevention.METHODSIndividuals with OPLs, but who were otherwise healthy and without diabetes, underwent pretreatment and posttreatment clinical exam and biopsy. Participants received metformin for 12 weeks (week 1, 500 mg; week 2, 1000 mg; weeks 3-12, 2000 mg daily). Pretreatment and posttreatment biopsies, saliva, and blood were obtained for biomarker analysis, including IHC assessment of mTOR signaling and exome sequencing.RESULTSTwenty-three participants were evaluable for response. The clinical response rate (defined as a ≥50% reduction in lesion size) was 17%. Although lower than the proposed threshold for favorable clinical response, the histological response rate (improvement in histological grade) was 60%, including 17% complete responses and 43% partial responses. Logistic regression analysis revealed that when compared with never smokers, current and former smokers had statistically significantly increased histological responses (P = 0.016). Remarkably, a significant correlation existed between decreased mTOR activity (pS6 IHC staining) in the basal epithelial layers of OPLs and the histological (P = 0.04) and clinical (P = 0.01) responses.CONCLUSIONTo our knowledge this is the first phase II trial of metformin in individuals with OPLs, providing evidence that metformin administration results in encouraging histological responses and mTOR pathway modulation, thus supporting its further investigation as a chemopreventive agent.TRIAL REGISTRATIONNCT02581137FUNDINGNIH contract HHSN261201200031I, grants R01DE026644 and R01DE026870.
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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.