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Repurposing metformin for the treatment of gastrointestinal cancer
Ademar Dantas Cunha Júnior1, Arinilda Campos Bragagnoli2, Felipe Osório Costa1
1Department of Internal Medicine, Division of Oncology, University of Campinas (UNICAMP), Campinas 13083-970, São Paulo, Brazil.
Abstract:
Diabetes mellitus type 2 and cancer share many risk factors. The pleiotropic insulin-dependent and insulin-independent effects of metformin might inhibit pathways that are frequently amplified in neoplastic tissue. Particularly, modulation of inflammation, metabolism, and cell cycle arrest are potential therapeutic cancer targets utilized by metformin to boost the anti-cancer effects of chemotherapy. Studies in vitro and in vivo models have demonstrated the potential of metformin as a chemo- and radiosensitizer, besides its chemopreventive and direct therapeutic activity in digestive system (DS) tumors. Hence, these aspects have been considered in many cancer clinical trials. Case-control and cohort studies and associated meta-analyses have evaluated DS cancer risk and metformin usage, especially in colorectal cancer, pancreatic cancer, and hepatocellular carcinoma. Most clinical studies have demonstrated the protective role of metformin in the risk for DS cancers and survival rates. On the other hand, the ability of metformin to enhance the actions of chemotherapy for gastric and biliary cancers is yet to be investigated. This article reviews the current findings on the anti-cancer mechanisms of metformin and its apparatus from pre-clinical and ongoing studies in DS malignancies.
Insights
Metformin, a diabetes drug, shows promise in cancer treatment by potentially inhibiting tumor growth and enhancing chemotherapy effectiveness. Research indicates its protective role in digestive system cancers, with ongoing studies exploring its full anti-cancer potential.
Area of Science:
- Oncology
- Endocrinology
- Pharmacology
Background:
- Type 2 diabetes and cancer share common risk factors.
- Metformin possesses pleiotropic effects, influencing both insulin-dependent and independent pathways.
- These pathways are often dysregulated in neoplastic tissues, suggesting metformin's potential anti-cancer role.
Purpose of the Study:
- To review the anti-cancer mechanisms of metformin.
- To explore metformin's therapeutic potential in digestive system (DS) malignancies.
- To summarize findings from pre-clinical and clinical studies on metformin's role in cancer.
Main Methods:
- Review of in vitro and in vivo studies on metformin's anti-cancer activity.
- Analysis of case-control, cohort studies, and meta-analyses on metformin and DS cancer risk.
- Evaluation of clinical trial data regarding metformin's chemopreventive and therapeutic effects.
Main Results:
- Metformin demonstrates potential as a chemo- and radiosensitizer.
- Studies suggest metformin has chemopreventive and direct therapeutic activity in DS tumors.
- Clinical data indicate a protective role for metformin in DS cancer risk and improved survival rates, particularly in colorectal, pancreatic, and liver cancers.
Conclusions:
- Metformin's modulation of inflammation, metabolism, and cell cycle arrest are key anti-cancer mechanisms.
- Further investigation is needed for gastric and biliary cancers regarding metformin's ability to enhance chemotherapy.
- Metformin shows significant promise as an adjunct therapy in managing digestive system cancers.
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