Metformin: The Answer to Cancer in a Flower? Current Knowledge and Future Prospects of Metformin as an Anti-Cancer Agent in Breast Cancer
Open accessAbstract
Interest has grown in studying the possible use of well-known anti-diabetic drugs as anti-cancer agents individually or in combination with, frequently used, chemotherapeutic agents and/or radiation, owing to the fact that diabetes heightens the risk, incidence, and rapid progression of cancers, including breast cancer, in an individual. In this regard, metformin (1, 1-dimethylbiguanide), well known as 'Glucophage' among diabetics, was reported to be cancer preventive while also being a potent anti-proliferative and anti-cancer agent. While meta-analysis studies reported a lower risk and incidence of breast cancer among diabetic individuals on a metformin treatment regimen, several in vitro, pre-clinical, and clinical studies reported the efficacy of using metformin individually as an anti-cancer/anti-tumor agent or in combination with chemotherapeutic drugs or radiation in the treatment of different forms of breast cancer. However, unanswered questions remain with regards to areas such as cancer treatment specific therapeutic dosing of metformin, specificity to cancer cells at high concentrations, resistance to metformin therapy, efficacy of combinatory therapeutic approaches, post-therapeutic relapse of the disease, and efficacy in cancer prevention in non-diabetic individuals. In the current article, we discuss the biology of metformin and its molecular mechanism of action, the existing cellular, pre-clinical, and clinical studies that have tested the anti-tumor potential of metformin as a potential anti-cancer/anti-tumor agent in breast cancer therapy, and outline the future prospects and directions for a better understanding and re-purposing of metformin as an anti-cancer drug in the treatment of breast cancer.
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High expression levels of influx transporters in cells might allow much higher accumulation of metformin resulting in selective toxicity and cell death as postulated to explain anti-cancer effects.
“A high expression levels of influx transporters in cells might allow a much higher accumulation of metformin resulting in selective toxicity and cell death as has been postulated to explain the anti-cancer effects of the drug (158).”
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 [158]
The metabolic changes that occur as a result of diabetes (hyperinsulinemia, hyperglycemia, and dyslipidemia) potentiate signaling pathways and may increase the oncogenic nature of breast tissue through accelerating cell growth and migration, angiogenesis, increasing metastasis, and decreasing the response to chemotherapy.
“The metabolic changes that occur as a result of diabetes (hyperinsulinemia, hyperglycemia, and dyslipidemia) potentiate signaling pathways and may increase the oncogenic nature of breast tissue through accelerating cell growth and migration, angiogenesis, increasing metastasis, and decreasing the response to chemotherapy (158, 244–247).”
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 [158]
An argument to explain the selective action of metformin in some cancers but not all is that there is a differential expression of the influx and efflux transporters in tumor cells that allows for the intracellular accumulation of metformin in the cancer cell and resultant selective toxicity.
“An argument to explain the selective action of metformin in some cancers but not all is that there is a differential expression of the influx and efflux transporters in tumor cells that allows for the intracellular accumulation of metformin in the cancer cell and resultant selective toxicity (158).”
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 [158]
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References 232 · Cited by 81
- Authors
- Samuel, S., Varghese, E., Kubatka, P., Triggle, C., & Büsselberg, D.
- Affiliations
- Weill Cornell Medical College in Qatar (QA)
- Comenius University Bratislava (SK)
- Corresponding author
- Samuel, Samson
- Büsselberg, Dietrich
- Venue
- Biomolecules
- Publisher
- MDPI AG
- Published
- 2019-12-09
- Volume
- 9
- Issue
- 12
- Pages
- 846
- ISSN
- 2218-273X (ISSN-L)
- PMC
- PMC6995629
- OpenAlex
- W2993007827
- Cited by
- 81
- References
- 232
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 7 · 2023: 13 · 2022: 14 · 2021: 20 · 2020: 14 · 2019: 1 · 2018: 2
- FWCI
- 1.08
- Type
- journal article
- Language
- en
- Open access
- gold
- dx.doi.org
- Licence
- Locations
- Biomolecules (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Figshare (submittedVersion, cc-by)
- Funders
- Qatar National Research Fund (NPRP 11S-1214-170101)
- 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, breast cancer, anticancer drug repurposing, biguanides, diabetes and cancer risk, combination chemotherapy, radiotherapy, metformin resistance, cancer prevention, molecular mechanisms of action, antiproliferative activity
- MeSH terms
- Antineoplastic Agents, Antineoplastic Combined Chemotherapy Protocols, Biological Products, Breast Neoplasms, Female, Humans, Hypoglycemic Agents, Metformin, Plant Extracts, Drug Resistance, Neoplasm, Galega, Cell Line, Tumor, Cell Proliferation
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