ArticleScientific reports2016
Toward Repurposing Metformin as a Precision Anti-Cancer Therapy Using Structural Systems Pharmacology.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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.
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Who cites it
24 citing papers in PubMed, 45 citations in OpenAlex.
- AI-driven computational drug design: tools, workflow and challenges.RSC advances · 2026Review
- Network toxicology-driven repurposing of metformin for hepatocellular carcinoma: insights from molecular docking and dynamics simulations.Journal of molecular modeling · 2026Article
- Therapeutic Switching of Metformin Using Heteroleptic Cu(II) and Zn(II) Complexes: A Combined Experimental and Computational Study.ACS omega · 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 for cancer therapy.Signal transduction and targeted therapy · 2024Review
- Phosphoproteomic analysis of metformin signaling in colorectal cancer cells elucidates mechanism of action and potential therapeutic opportunities.Clinical and translational medicine · 2023Article
- Drug repurposing: re-inventing therapies for cancer without re-entering the development pipeline-a review.Journal of the Egyptian National Cancer Institute · 2022Review
- Emerging Promise of Computational Techniques in Anti-Cancer Research: At a Glance.Bioengineering (Basel, Switzerland) · 2022Review
- Metformin Downregulates the Expression of Epidermal Growth Factor Receptor Independent of Lowering Blood Glucose in Oral Squamous Cell Carcinoma.Frontiers in endocrinology · 2022Article
- Immunotherapy in endometrial cancer: rationale, practice and perspectives.Biomarker research · 2021Review
- Metformin and Bone Metabolism in Endogenous Glucocorticoid Excess: An Exploratory Study.Frontiers in endocrinology · 2021Article
- Receptor tyrosine kinase targeting in glioblastoma: performance, limitations and future approaches.Contemporary oncology (Poznan, Poland) · 2020Review
- The RANK-RANKL axis: an opportunity for drug repurposing in cancer?Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2019Review
- Systems biology and network pharmacology of frailty reveal novel epigenetic targets and mechanisms.Scientific reports · 2019Article
- Systems Bioinformatics: increasing precision of computational diagnostics and therapeutics through network-based approaches.Briefings in bioinformatics · 2019Review
- Identifying Protein Features Responsible for Improved Drug Repurposing Accuracies Using the CANDO Platform: Implications for Drug Design.Molecules (Basel, Switzerland) · 2019Article
- Drug Repositioning Inferred from E2F1-Coregulator Interactions Studies for the Prevention and Treatment of Metastatic Cancers.Theranostics · 2019Article
- Drug repurposing for the treatment of glioblastoma multiforme.Journal of experimental & clinical cancer research : CR · 2017Review
- VariFunNet, an integrated multiscale modeling framework to study the effects of rare non-coding variants in Genome-Wide Association Studies: applied to Alzheimer's Disease.Proceedings. IEEE International Conference on Bioinformatics and Biomedicine · 2017Article
- MeSHDD: Literature-based drug-drug similarity for drug repositioning.Journal of the American Medical Informatics Association : JAMIA · 2017Article
Corrections and comments
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Authors and funding
6 authors at 5 institutions in 2 countries.
Funding
Abstract
Metformin, a drug prescribed to treat type-2 diabetes, exhibits anti-cancer effects in a portion of patients, but the direct molecular and genetic interactions leading to this pleiotropic effect have not yet been fully explored. To repurpose metformin as a precision anti-cancer therapy, we have developed a novel structural systems pharmacology approach to elucidate metformin's molecular basis and genetic biomarkers of action. We integrated structural proteome-scale drug target identification with network biology analysis by combining structural genomic, functional genomic, and interactomic data. Through searching the human structural proteome, we identified twenty putative metformin binding targets and their interaction models. We experimentally verified the interactions between metformin and our top-ranked kinase targets. Notably, kinases, particularly SGK1 and EGFR were identified as key molecular targets of metformin. Subsequently, we linked these putative binding targets to genes that do not directly bind to metformin but whose expressions are altered by metformin through protein-protein interactions, and identified network biomarkers of phenotypic response of metformin. The molecular targets and the key nodes in genetic networks are largely consistent with the existing experimental evidence. Their interactions can be affected by the observed cancer mutations. This study will shed new light into repurposing metformin for safe, effective, personalized therapies.
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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.