ArticleCancer prevention research (Philadelphia, Pa.)2012
Metformin prevents liver tumorigenesis by inhibiting pathways driving hepatic lipogenesis.
Article in Cancer prevention research (Philadelphia, Pa.), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers, 4 of them syntheses that pooled it.
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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.
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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
84 citing papers in PubMed, 4 syntheses or guidelines pooled it, 147 citations in OpenAlex.
- Diabetes medications and cancer risk associations: a systematic review and meta-analysis of evidence over the past 10 years.Scientific reports · 2023Pooled it
- Anti-hyperlipidemia of garlic by reducing the level of total cholesterol and low-density lipoprotein: A meta-analysis.Medicine · 2018Pooled it
- Anti-tumor effects of metformin in animal models of hepatocellular carcinoma: a systematic review and meta-analysis.PloS one · 2015Pooled it
- Metformin and cancer risk and mortality: a systematic review and meta-analysis taking into account biases and confounders.Cancer prevention research (Philadelphia, Pa.) · 2014 · on this mapPooled it
- Anti-Inflammatory Effects of Metformin Irrespective of Diabetes Status.Circulation research · 2016Trial
- From diabetes to tumor growth: unravelling the impact of glucose-lowering therapies.Endocrine · 2026Review
- Constitutive AMPK activation prevents hepatocellular carcinoma development through inhibition of HNF4α activity.Science advances · 2026Article
- Modulatory effect of metformin and its transporters on immune infiltration in tumor microenvironment: a bioinformatic study with experimental validation.Discover oncology · 2025Article
- Drug Repurposing: A Conduit to Unravelling Metabolic Reprogramming for Cancer Treatment.Mini reviews in medicinal chemistry · 2025Review
- Metformin upregulates circadian gene PER2 to inhibit growth and enhance the sensitivity of glioblastoma cell lines to radiotherapy via SIRT2/G6PD pathway.Frontiers in pharmacology · 2025Article
- Review
- Regulation and targeting of SREBP-1 in hepatocellular carcinoma.Cancer metastasis reviews · 2024Review
- Metformin: A Dual-Role Player in Cancer Treatment and Prevention.International journal of molecular sciences · 2024Review
- Characterization of stem cell subtypes and prognostic signature in hepatocellular carcinoma.Journal of cancer research and clinical oncology · 2023Article
- Antitumor Activity of Metformin Combined with Locoregional Therapy for Liver Cancer: Evidence and Future Directions.Cancers · 2023Review
- A pilot metabolomic study of drug interaction with the immune response to seasonal influenza vaccination.NPJ vaccines · 2023Article
- Metformin Induces Lipogenesis and Apoptosis in H4IIE Hepatocellular Carcinoma Cells.Development & reproduction · 2023Article
- Role of metformin in the diagnosis, prevention, and treatment of hepatocellular carcinoma.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2022Article
- Immunometabolic factors contributing to obesity-linked hepatocellular carcinoma.Frontiers in cell and developmental biology · 2022Review
- Plasma lipids, tumor parameters and survival in HCC patients with HBV and HCV.Journal of translational science · 2021Article
24 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
A number of factors have been identified that increase the risk of hepatocellular carcinoma (HCC). Recently it has become appreciated that type II diabetes increases the risk of developing HCC. This represents a patient population that can be identified and targeted for cancer prevention. The biguanide metformin is a first-line therapy for the treatment of type II diabetes in which it exerts its effects primarily on the liver. A role of metformin in HCC is suggested by studies linking metformin intake for control of diabetes with a reduced risk of HCC. Although a number of preclinical studies show the anticancer properties of metformin in a number of tissues, no studies have directly examined the effect of metformin on preventing carcinogenesis in the liver, one of its main sites of action. We show in these studies that metformin protected mice against chemically induced liver tumors. Interestingly, metformin did not increase AMPK activation, often shown to be a metformin target. Rather metformin decreased the expression of several lipogenic enzymes and lipogenesis. In addition, restoring lipogenic gene expression by ectopic expression of the lipogenic transcription factor SREBP1c rescues metformin-mediated growth inhibition. This mechanism of action suggests that metformin may also be useful for patients with other disorders associated with HCC in which increased lipid synthesis is observed. As a whole these studies show that metformin prevents HCC and that metformin should be evaluated as a preventive agent for HCC in readily identifiable at-risk patients.
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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.