Trial reportThe Laryngoscope2017
Metformin effects on head and neck squamous carcinoma microenvironment: Window of opportunity trial.
Trial report in The Laryngoscope, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 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
39 citing papers in PubMed, 67 citations in OpenAlex.
- A Phase II Feasibility Study Combining Pembrolizumab and Metformin in Patients with Metastatic Head and Neck Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Trial
- Phase II trial of nivolumab and metformin in patients with treatment-refractory microsatellite stable metastatic colorectal cancer.Journal for immunotherapy of cancer · 2023Trial
- p53 and p21 Status Influences Cellular Response to Metformin inCurrent issues in molecular biology · 2026Article
- Global research dynamics in metabolic biomarkers and cancer: a bibliometric study from 2015 to 2025.Discover oncology · 2025Review
- Biological Anti-Tumoral Mechanisms of Metformin in Head and Neck Squamous Cell Carcinomas: A Systematic Review.Journal of clinical medicine · 2025Review
- Antitumor Effects of Metformin in Squamous Cell Carcinoma under Leptin Treatment Conditions.Preventive nutrition and food science · 2025Article
- Tumor Microenvironment Lactate: Is It a Cancer Progression Marker, Immunosuppressant, and Therapeutic Target?Molecules (Basel, Switzerland) · 2025Review
- Integrative single-cell and bulk RNA-seq analysis identifies lactylation-related signature in osteosarcoma.Functional & integrative genomics · 2025Article
- A Narrative Review of Prognostic Gene Signatures in Oral Squamous Cell Carcinoma Using LASSO Cox Regression.Biomedicines · 2025Review
- Two by Two Factorial Design using Metformin and Curcumin for Second Primary Head and Neck Cancer Prevention Trial.Asian Pacific journal of cancer prevention : APJCP · 2024Article
- The Metformin Immunoregulatory Actions in Tumor Suppression and Normal Tissues Protection.Current medicinal chemistry · 2024Review
- Metformin and its potential influence on cell fate decision between apoptosis and senescence in cancer, with a special emphasis on glioblastoma.Frontiers in oncology · 2024Review
- The Impact of Metformin on Tumor-Infiltrated Immune Cells: Preclinical and Clinical Studies.International journal of molecular sciences · 2023Review
- Metformin and cancer hallmarks: shedding new lights on therapeutic repurposing.Journal of translational medicine · 2023Review
- Is it still worth pursuing the repurposing of metformin as a cancer therapeutic?British journal of cancer · 2023Review
- Metformin increases natural killer cell functions in head and neck squamous cell carcinoma through CXCL1 inhibition.Journal for immunotherapy of cancer · 2022Article
- Targeting of the tumor immune microenvironment by metformin.Journal of cell communication and signaling · 2022Review
- The promising therapeutic effects of metformin on metabolic reprogramming of cancer-associated fibroblasts in solid tumors.Cellular & molecular biology letters · 2022Article
- STAT3 pathway in cancers: Past, present, and future.MedComm · 2022Review
- Metformin and Cancer, an Ambiguanidous Relationship.Pharmaceuticals (Basel, Switzerland) · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 4 institutions in 1 country.
Funding
Abstract
objectiveThe tumor microenvironment frequently displays abnormal cellular metabolism, which contributes to aggressive behavior. Metformin inhibits mitochondrial oxidative phosphorylation, altering metabolism. Though the mechanism is unclear, epidemiologic studies show an association between metformin use and improved outcomes in head and neck squamous cell carcinoma (HNSCC). We sought to determine if metformin alters metabolism and apoptosis in HNSCC tumors. STUDY
designWindow of opportunity trial of metformin between diagnostic biopsy and resection. Participants were patients with newly diagnosed HNSCC. Fifty patients were enrolled, and 39 completed a full-treatment course. Metformin was titrated to standard diabetic dose (2,000 mg/day) for a course of 9 or more days prior to surgery.
methodsImmunohistochemistry (IHC) for the metabolic markers caveolin-1 (CAV1), B-galactosidase (GALB), and monocarboxylate transporter 4 (MCT4), as well as the Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) apoptosis assay and Ki-67 IHC, were performed in pre- and postmetformin specimens. Exploratory mass spectroscopy imaging (MSI) to assess lactate levels also was performed in three subjects.
resultsMetformin was well tolerated. The average treatment course was 13.6 days. Posttreatment specimens showed a significant increase in stromal CAV1 (P < 0.001) and GALB (P < 0.005), as well as tumor cell apoptosis by TUNEL assay (P < 0.001). There was no significant change in stromal MCT4 expression or proliferation measured by Ki67. Lactate levels in carcinoma cells were increased 2.4-fold postmetformin (P < 0.05), as measured by MSI.
conclusionMetformin increases markers of reduced catabolism and increases senescence in stromal cells as well as carcinoma cell apoptosis. This study demonstrates that metformin modulates metabolism in the HNSCC microenvironment. LEVEL OF EVIDENCE: 4. Laryngoscope, 127:1808-1815, 2017.
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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.