Metformin Targets Multiple Signaling Pathways in Cancer
Open accessAbstract
Metformin, an inexpensive and well-tolerated oral agent commonly used in the first-line treatment of type 2 diabetes, has become the focus of intense research as a candidate anticancer agent. Here, we discuss the potential of metformin in cancer therapeutics, particularly its functions in multiple signaling pathways, including AMP-activated protein kinase, mammalian target of rapamycin, insulin-like growth factor, c-Jun N-terminal kinase/mitogen-activated protein kinase (p38 MAPK), human epidermal growth factor receptor-2, and nuclear factor kappaB pathways. In addition, cutting-edge targeting of cancer stem cells by metformin is summarized.
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These metabolic pathways, rather than a direct anti-proliferative action, may be the primary target of metformin as metformin decreases hepatic gluconeogenesis, improves insulin sensitivity, reduces insulin and blood glucose levels, and these effects also reduce tumor growth.
“These metabolic pathways, rather than a direct anti-proliferative action, may be the target as Metformin decreases hepatic gluconeogenesis, improves insulin sensitivity, reduces insulin and blood glucose levels, and these effects, which also will reduce tumor growth, rather than a direct anti-proliferative action may be the primary target of metformin (55, 248).”
From A Critical Review of the Evidence That Metformin Is a Putative Anti-Aging Drug That Enhances Healthspan and Extends Lifespan (2021) · cites this paper as [248]
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References 129 · Cited by 152
- Authors
- Lei, Y., Yi, Y., Liu, Y., Liu, X., Keller, E. T., Qian, C.-N., Zhang, J., & Lu, Y.
- Affiliations
- Guangxi Medical University (CN)
- University of Michigan (US)
- Sun Yat-sen University Cancer Center (CN)
- Corresponding author
- Zhang, Jian
- Venue
- Chinese Journal of Cancer
- Published
- 2017-01-26
- Volume
- 36
- Issue
- 1
- Pages
- 17-17
- ISSN
- 1000-467X (ISSN-L)
- 1944-446X
- PMC
- PMC5270304
- OpenAlex
- W2582810155
- Cited by
- 152
- References
- 129
- Citations by year
- 2026: 6 · 2025: 17 · 2024: 14 · 2023: 20 · 2022: 24 · 2021: 19 · 2020: 14 · 2019: 19 · 2018: 14 · 2017: 5
- FWCI
- 1.33
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- 癌症：英文版 (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Deep Blue (University of Michigan) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China (81130046, 81171993, 81272415)
- Guangxi Key Project (2013GXNSFEA053004)
- Guangxi Projects (1355004-5, 2012GXNSFCB053004)
- 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, anticancer agents, AMPK, mTOR, insulin-like growth factor, p38 MAPK, HER2, NF-κB, cancer stem cells, signaling pathways, type 2 diabetes
- MeSH terms
- Animals, Antineoplastic Agents, Humans, Hypoglycemic Agents, Metformin, Neoplasms, Neoplastic Stem Cells, Signal Transduction
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