The DOI matches its Crossref record; 55 of the 56 references it cites were found in a registry or an index.
Metformin and Other Biguanides in Oncology: Advancing the Research Agenda
Open accessPublished version of a preprint
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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Cites
Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin
(2002) · New England Journal of Medicine · doi:10.1056/nejmoa012512 · Cited by 19,011
AMPK Phosphorylation of Raptor Mediates a Metabolic Checkpoint
Gwinn, D. M., Shackelford, D. B., Egan, D. F., Mihaylova, M. M., Mery, A., Vasquez, D. S., Turk, B. E., & Shaw, R. J. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.03.003 · Cited by 3,849
Kahn, B. B., Alquier, T., Carling, D., & Hardie, D. G. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2004.12.003 · Cited by 2,799
Giovannucci, E., Harlan, D. M., Archer, M. C., Bergenstal, R. M., Gapstur, S. M., Habel, L. A., Pollak, M., Regensteiner, J. G., & Yee, D. (2010) · Diabetes Care · doi:10.2337/dc10-0666 · Cited by 2,366
Self-citationInsulin and insulin-like growth factor signalling in neoplasia
Pollak, M. (2008) · Nature Reviews Cancer · doi:10.1038/nrc2536 · Cited by 2,059
Self-citationThe Kinase LKB1 Mediates Glucose Homeostasis in Liver and Therapeutic Effects of Metformin
Shaw, R. J., Lamia, K. A., Vasquez, D., Koo, S.-H., Bardeesy, N., DePinho, R. A., Montminy, M., & Cantley, L. C. (2005) · Science · doi:10.1126/science.1120781 · Cited by 1,950
The LKB1-AMPK pathway: metabolism and growth control in tumour suppression
Shackelford, D. B., & Shaw, R. J. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2676 · Cited by 1,943
Shaw, R. J., Kosmatka, M., Bardeesy, N., Hurley, R. L., Witters, L. A., DePinho, R. A., & Cantley, L. C. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0308061100 · Cited by 1,797
Bailey, C. J., & Turner, R. C. (1996) · New England Journal of Medicine · doi:10.1056/nejm199602293340906 · Cited by 1,726
AMP-kinase regulates food intake by responding to hormonal and nutrient signals in the hypothalamus
Minokoshi, Y., Alquier, T., Furukawa, N., Kim, Y.-B., Lee, A., Xue, B., Mu, J., Foufelle, F., Ferré, P., Birnbaum, M. J., et al. (2004) · Nature · doi:10.1038/nature02440 · Cited by 1,637
Cited by
Sorted by citations
Targeting cancer metabolism: a therapeutic window opens
Heiden, M. G. V. (2011) · Nature Reviews Drug Discovery · doi:10.1038/nrd3504 · Cited by 1,443
The insulin and insulin-like growth factor receptor family in neoplasia: an update
Pollak, M. (2012) · Nature Reviews Cancer · doi:10.1038/nrc3215 · Cited by 1,116
Self-citationSuppression of insulin feedback enhances the efficacy of PI3K inhibitors
Hopkins, B. D., Pauli, C., Du, X., Wang, D. G., Li, X., Wu, D., Amadiume, S. C., Goncalves, M. D., Hodakoski, C., Lundquist, M. R., et al. (2018) · Nature · doi:10.1038/s41586-018-0343-4 · Cited by 706
Moiseeva, O., Deschênes‐Simard, X., St‐Germain, E., Igelmann, S., Huot, G., Cadar, A. E., Bourdeau, V., Pollak, M. N., & Ferbeyre, G. (2013) · Aging Cell · doi:10.1111/acel.12075 · Cited by 654
“Epidemiological and laboratory studies have suggested that metformin has antineoplastic activity (Memmott et al., 2010; Pollak, 2010; Bhalla et al., 2012; Pollak, 2012).”
BackgroundInfluentialSelf-citationShackelford, D. B., Abt, E., Gerken, L., Vasquez, D. S., Seki, A., Leblanc, M., Wei, L., Fishbein, M. C., Czernin, J., Mischel, P. S., et al. (2013) · Cancer Cell · doi:10.1016/j.ccr.2012.12.008 · Cited by 585
“In addition, a non-cell-autonomous mechanism for metformin's antitumor effects may be its ability to lower circulating blood glucose and insulin levels, which also contribute to cancer risk and incidence in some contexts (Pollak, 2010).”
Influential
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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