ArticleOncotarget2015
Hyperglycemia-induced metabolic compensation inhibits metformin sensitivity in ovarian cancer.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
31 citing papers in PubMed, 39 citations in OpenAlex.
- Metabolic sensor AMPK licenses intestinal CD103Science advances · 2026Article
- Effectiveness of Metformin in Preventing Colorectal Cancer Among Japanese Patients With Type 2 Diabetes: A Target Trial Emulation.Pharmacoepidemiology and drug safety · 2026Article
- Drug repurposing in oncology: a path beyond the bottleneck.Medical oncology (Northwood, London, England) · 2025Review
- O-GlcNAcylation in ovarian tumorigenesis and its therapeutic implications.Translational oncology · 2025Review
- Enhancing Immunotherapy in Ovarian Cancer: The Emerging Role of Metformin and Statins.International journal of molecular sciences · 2023Review
- Metformin and cancer hallmarks: shedding new lights on therapeutic repurposing.Journal of translational medicine · 2023Review
- Sensitizing tumors to anti-PD-1 therapy by promoting NK and CD8+ T cells via pharmacological activation of FOXO3.Journal for immunotherapy of cancer · 2021Article
- High glucose: an emerging association between diabetes mellitus and cancer progression.Journal of molecular medicine (Berlin, Germany) · 2021Review
- Therapeutic Repurposing of Biguanides in Cancer.Trends in cancer · 2021Review
- The Role of Metformin in Ovarian Cancer: Does Metformin Increase Survival in Ovarian Neoplasm?Cureus · 2021Review
- Possible Role of Metformin as an Immune Modulator in the Tumor Microenvironment of Ovarian Cancer.International journal of molecular sciences · 2021Review
- Low glucose enhanced metformin's inhibitory effect on pancreatic cancer cells by suppressing glycolysis and inducing energy stress via up-regulation of miR-210-5p.Cell cycle (Georgetown, Tex.) · 2020Article
- Anti-Angiogenic Effects of Phytochemicals on miRNA Regulating Breast Cancer Progression.Biomolecules · 2020Review
- Hypoxia and hyperglycaemia determine why some endometrial tumours fail to respond to metformin.British journal of cancer · 2020Article
- Article
- SPHK1 Is a Novel Target of Metformin in Ovarian Cancer.Molecular cancer research : MCR · 2019Article
- Reversal of obesity-driven aggressiveness of endometrial cancer by metformin.American journal of cancer research · 2019Article
- Pleiotropic Effects of Metformin on Cancer.International journal of molecular sciences · 2018Review
- Metformin inhibits ovarian cancer via decreasing H3K27 trimethylation.International journal of oncology · 2018Article
- Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Increasing interest in repurposing the diabetic medication metformin for cancer treatment has raised important questions about the translation of promising preclinical findings to therapeutic efficacy, especially in non-diabetic patients. A significant limitation of the findings to date is the use of supraphysiologic metformin doses and hyperglycemic conditions in vitro. Our goals were to determine the impact of hyperglycemia on metformin response and to address the applicability of metformin as a cancer therapeutic in non-diabetic patients. In normoglycemic conditions, lower concentrations of metformin were required to inhibit cell viability, while metformin treatment in hyperglycemic conditions resulted in increased glucose uptake and glycolytic flux, contributing to cell survival. Mechanistically, maintenance of c-Myc expression under conditions of hyperglycemia or via gene amplification facilitated metabolic escape from the effects of metformin. In vivo, treatment of an ovarian cancer mouse model with metformin resulted in greater tumor weight reduction in normoglycemic vs. hyperglycemic mice, with increased c-Myc expression observed in metformin-treated hyperglycemic mice. These findings indicate that hyperglycemia inhibits the anti-cancer effects of metformin in vitro and in vivo. Furthermore, our results suggest that metformin may elicit stronger responses in normoglycemic vs. hyperglycemic patients, highlighting the need for prospective clinical testing in patients without diabetes.
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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.