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Metformin and Other Biguanides in Oncology: Advancing the Research Agenda
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Abstract
Retrospective studies that may be impractical to confirm prospectively suggest that diabetics treated with metformin have a substantially reduced cancer burden compared with other diabetics. It is unclear if this reflects a chemopreventive effect, an effect on transformed cells, or both. It also remains to be established if these data have relevance to people without diabetes. Laboratory models, however, provide independent impressive evidence for the activity of metformin and other biguanides in both cancer treatment and chemoprevention. Investigations of mechanisms of action of biguanides have revealed considerable complexity and have identified important gaps in knowledge that should be addressed to ensure the optimal design of clinical trials of these agents. Such trials may define important new indications for biguanides in the prevention and/or treatment of many common cancers. Cancer Prev Res; 3(9); 1060–5. ©2010 AACR.
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“However, our results indicate that PTEN-negative tumors seem resistant to the anticancer effect of metformin, which may be related to another anticancer mechanism of metformin involving adenosine monophosphate-activated protein kinase (AMPK) [3,18].”
From Enzalutamide Plus Metformin Versus Enzalutamide Alone in Metastatic Castration-resistant Prostate Cancer: A Randomized Phase 2 Trial (SAKK 08/14). (2026) · cites this paper as [18]
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Cerella, C., Michiels, C., Dashwood, R. H., Surh, Y., & Diederich, M. F. (2013) · International Journal of Cell Biology · doi:10.1155/2013/293201 · Cited by 6
The Role of Diabetes and Diabetes Treatments in Colorectal Cancer Mortality, Incidence, and Survival
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Lifestyle: Breaking the cancer habit
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“Metformin may also increase AMPK activity in cancer cells, leading to downstream effects that include inhibition of mammalian target of rapamycin signaling.(10,22) Population-based studies suggest that patients with diabetes who are treated with metformin have a lower risk of breast cancer.”
BackgroundThompson, M. D., Lubet, R. A., McCormick, D. L., Clapper, M. L., Bode, A. M., Juliana, M. M., Moeinpour, F. L., & Grubbs, C. J. (2017) · Oncology Letters · doi:10.3892/ol.2017.6632 · Cited by 5
“Thus there are multiple direct and indirect mechanisms by which metformin may target cancer cells (19,20).”
BackgroundTakano, K., Hachiya, A., Murase, D., Kawasaki, A., Uda, H., Kasamatsu, S., Sugai, Y., Takahashi, Y., Hase, T., Ohuchi, A., et al. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21041451 · Cited by 5
“While the activation of AMPK and inhibition of the mitochondrial electron transfer system are known modes of action of biguanide compounds [29], the involvement of AMPK independent pathways has also been recently reported depending on physiological actions [30].”
BackgroundMetformin to Prevent Prostate Cancer: A Call to Unite
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“Published by Elsevier include direct effects (on the tumor andmicroenvironment) and indirect effects (on the host that may influence the tumor) [4].”
BackgroundA novel biguanide (IM1761065) inhibits bioenergetics of glioblastoma tumorspheres
Roh, T. H., Lee, J.-H., Kim, S. J., Shim, J., Park, J., Yoon, S., Teo, W., Kim, S. H., Chang, J. H., & Kang, S. (2021) · Journal of Neuro-Oncology · doi:10.1007/s11060-021-03903-7 · Cited by 4
“These patients treated with the representative biguanide, metformin, have a relatively low incidence of cancer [10, 14].”
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“It has been known for several years that molecules of the biguanide family, such as metformin and phenformin, are of potential interest in oncology [21].”
BackgroundGillessen, S., Gobat, K., Cathomas, R., Fischer, N., Pereira Mestre, R., Hermanns, T., Rothschild, S. I., Mach, N., Mingrone, W., Ciriolo, M., et al. (2026) · European Urology Oncology · doi:10.1016/j.euo.2026.03.001 · Cited by 4
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“11,20 This study builds on these findings by showing that combining stool transplantation and metformin produces complementary effects, reducing bacterial abundance and suppressing inflammation to attenuate polyp formation.”
Azar, J. A., Bassil, M., Irani, J., Badawi, K. A., Sawan, C., Moussa, M., Hakimeh, N., & Abboud, E. (2018) · Journal of Biomedical Sciencies · doi:10.4172/2254-609x.100093 · Cited by 2
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“Several drugs used to treat type 2 diabetes such as metformin, can inhibit multiple pathways involved in cell growth, which may be associated with anticancer effects.(19,33) Moreover, BMI in the 2018 NRD database is a categorical variable, not a continuous type.”
BackgroundMetformin in breast cancer treatment
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“The pharmacokinetic and pharmacodynamic characteristics of each of them are caused by certain chemical diferences between them [32].”
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Obesity and Gastrointestinal Cancer-related Factor
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“학치료의 보조치료(adjuvant therapy)로 추가하는 유용성에 대한 연구가 진행 중이다.(28)”
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Metadata
- Authors
- Pollak, M.
- Affiliations
- Author's Affiliation: Department of Oncology, McGill University and Jewish General Hospital, Montreal, Quebec, Canada
- Venue
- Cancer Prevention Research
- Published
- 2010-09-01
- Volume
- 3
- Issue
- 9
- Pages
- 1060-1065
- ISSN
- 1940-6207 (ISSN-L)
- 1940-6215
- PMC
- PMC2954412
- OpenAlex
- W2165189414
- Cited by
- 240
- References
- 56
- Citations by year
- 2026: 12 · 2025: 3 · 2024: 6 · 2023: 8 · 2022: 7 · 2021: 9 · 2020: 5 · 2019: 12 · 2018: 11 · 2017: 11 · 2016: 8 · 2015: 23 · 2014: 14 · 2013: 23 · 2012: 44
- FWCI
- 3.12
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cancer Prevention Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Prostate Cancer Foundation
- McGill University
- Prostate Cancer Canada
- National Institutes of Health (5r01ca101008-02)
- Canadian Cancer Society Research Institute
- National Cancer Institute (R01 CA101008)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Keywords
- metformin, biguanides, chemoprevention, cancer therapy, diabetes mellitus, mechanism of action, clinical trial design, laboratory model
- MeSH terms
- Animals, Antineoplastic Agents, Biguanides, Humans, Hypoglycemic Agents, Medical Oncology, Metformin, Neoplasms, Biomedical Research
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