ArticleBreast cancer research and treatment2021
Metformin and an insulin/IGF-1 receptor inhibitor are synergistic in blocking growth of triple-negative breast cancer.
Article in Breast cancer research and treatment, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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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
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.
- PI3K/AKT/mTOR Targeting in Colorectal Cancer Radiotherapy: A Systematic Review.Journal of gastrointestinal cancer · 2025Pooled it
- Insulin Resistance and Cutaneous Squamous Cell Carcinoma: A Narrative Review of Molecular Mechanisms.Iranian journal of medical sciences · 2026Review
- Effects of nucleic acid metabolism on prognosis and immune invasion of triple-negative breast cancer.Genes and immunity · 2026Article
- Investigating the causal link between metformin and lung cancer risk: a two-sample mendelian randomization analysis.BMC cancer · 2026Article
- BNIP3 is a key driver of breast cancer progression and a novel glycolysis-regulating biomarker.Scientific reports · 2025Article
- Mendelian Randomization and Bioinformatics Analysis Reveal the Potential Protective Role of Metformin in Primary Liver Cancer.Food science & nutrition · 2025Article
- Metformin-Based Combination Approaches for Triple-Negative Breast Cancer.Pharmaceutics · 2025Review
- Metformin sensitizes triple-negative breast cancer to histone deacetylase inhibitors by targeting FGFR4.Journal of biomedical science · 2025Article
- Metformin induces ZFP36 by mTORC1 inhibition in cervical cancer-derived cell lines.BMC cancer · 2024Article
- Review
- A home-based lifestyle intervention program reduces the tumorigenic potential of triple-negative breast cancer cells.Scientific reports · 2024Article
- Article
- Development of a prognostic model related to homologous recombination deficiency in glioma based on multiple machine learning.Frontiers in immunology · 2024Article
- IGF-1R targeting in cancer - does sub-cellular localization matter?Journal of experimental & clinical cancer research : CR · 2023Review
- Antitumor Activity of Metformin Combined with Locoregional Therapy for Liver Cancer: Evidence and Future Directions.Cancers · 2023Review
- Dasatinib in combination with BMS-754807 induce synergistic cytotoxicity in lung cancer cells through inhibiting lung cancer cell growth, and inducing autophagy as well as cell cycle arrest at the G1 phase.Investigational new drugs · 2023Article
- Drugging IGF-1R in cancer: New insights and emerging opportunities.Genes & diseases · 2023Review
- Targeting of the tumor immune microenvironment by metformin.Journal of cell communication and signaling · 2022Review
- Knockdown of SNORA47 Inhibits the Tumorigenesis of NSCLCFrontiers in oncology · 2021Article
- Anticancer Benefit of Metformin in Patients With Early-Stage Pancreatic Cancer: A Retrospective Cohort Study.Technology in cancer research & treatmentArticle
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
purposeTriple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with poor survival outcomes. Metformin has been shown to have antitumor effects by lowering serum levels of the mitogen insulin and having pleiotropic effects on cancer cell signaling pathways. BMS-754807 is a potent and reversible inhibitor of both insulin-like growth factor 1 receptor (IGF-1R) and insulin receptor (IR). Both drugs have been reported to have some efficacy in TNBC. However, it is unclear whether the combination of the two drugs is more effective than single drug treatment in TNBC.
methodsWe treated a panel of TNBC cell lines with metformin and BMS-754807 alone and in combination and tested cell viability using MTS assays. We used the CompuSyn software to analyze for additivity, synergism, or antagonism. We also examined the molecular mechanism by performing reverse phase protein assay (RPPA) to detect the candidate pathways altered by single drugs and the drug combination and used Western blotting to verify and expand the findings.
resultsThe combination of metformin and BMS-754807 showed synergy in 11 out of 13 TNBC cell lines tested (85%). RPPA analysis detected significant alterations by the drug combination of multiple proteins known to regulate cell cycle and tumor growth. In particular, the drug combination significantly increased levels of total and phosphorylated forms of the cell cycle inhibitor p27
conclusionsWe conclude that the combination of metformin and BMS-754807 is more effective than either drug alone in inhibiting cell proliferation in the majority of TNBC cell lines, and that one important mechanism may be suppression of SCF
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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.