A Narrative Review: Repurposing Metformin as a Potential Therapeutic Agent for Oral Cancer
Abstract
:Simple Summary
Abstract
1. Introduction
2. Classical Application and Mechanism of Action of Metformin
3. Novel Applications for Metformin
3.1. Metformin’s Efficacy on the Cardiovascular System and Kidneys
3.2. Metformin’s Efficacy on Polycystic Ovary Syndrome (PCOS)
3.3. Metformin’s Efficacy on Cancer Treatment
4. The Therapy for Oral Cancer
4.1. Vitamin D
4.2. Target Drugs
4.3. Photothermal Therapy
5. Relations between Metformin and Oral Cancer
6. How Metformin Inhibits Oral Squamous Cell Carcinoma
Study | Study Design | Sample Size | Key Findings | Limitations |
---|---|---|---|---|
Mekala et al. [11] | Retrospective Study | 500 oral cancer patients, 500 controls | Metformin use is associated with a lower risk of oral cancer in diabetic patients | Potential for selection bias due to retrospective nature |
Hammad et al. [44] | Review Article | Multiple studies reviewed | Explores metformin’s applications in dentistry, particularly its potential to prevent oral cancer | Dependent on the quality and consistency of reviewed studies |
Wei et al. [91] | In vitro Study | OSCC cell lines | Metformin inhibits OSCC cell proliferation by interfering with NGFR-N and p53 pathways | In vitro findings need further validation in clinical settings |
Yin et al. [93] | Experimental Study | OSCC cell lines | Metformin inhibits EMT in OSCC via the mTOR/HIF-1α/PKM2/STAT3 pathway | Study limited to cell lines; clinical relevance requires more studies |
Chen et al. [99] | Experimental Study | In vitro and in vivo | LIN28 inhibitor combined with metformin reduces OSCC cell proliferation and migration | Preclinical study; human trials needed for confirmation |
Tseng [87] | Cohort Study | Large cohort of diabetic patients | Metformin significantly reduces the risk of oral cancer in patients with T2DM | Observational study design limits causal inferences |
Hu et al. [100] | Cohort Study | T2DM patients with OSCC | Metformin lowers EGFR expression and reduces the risk of OSCC recurrence | Observational nature limits the ability to establish causality |
Gupta et al. [105] | Case-Control Study | Oral cancer patients | Elevated vitamin B12 levels were observed in oral cancer patients; metformin might affect this interaction | Small sample size and observational design limit generalizability |
Broadfield et al. [16] | Experimental Study | In vivo and in vitro | Metformin modulates gut microbiome diversity, reducing tumor growth in colorectal cancer models | The direct applicability to oral cancer needs further exploration |
He et al. [104] | In vitro and in vivo | OSCC models | Metformin combined with 4SC-202 promotes apoptosis in OSCC cells | Preclinical study; further research needed to confirm in human trials |
7. The Challenge of Metformin in Oral Cancer
8. Risk of Bias Assessment
9. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Study | Study Design | Selection Bias | Information Bias | Reporting Bias | Other Biases | Overall Risk of Bias |
---|---|---|---|---|---|---|
Mekala et al. [11] | Retrospective Study | High | Moderate | Low | N/A | High |
Hammad et al. [44] | Review Article | Low | High | High | Dependent on included studies | High |
Wei et al. [91] | In vitro Study | N/A | Low | Moderate | Laboratory conditions | Moderate |
Yin et al. [93] | Experimental Study | N/A | Moderate | Low | Limited to cell lines | Moderate |
Chen et al. [99] | Experimental Study | N/A | Moderate | Low | Preclinical study design | Moderate |
Tseng [87] | Cohort Study | Moderate | Low | Low | Observational design | Moderate |
Hu et al. [100] | Cohort Study | Moderate | Low | Moderate | Observational design | Moderate |
Gupta et al. [105] | Case-Control Study | High | Moderate | High | Small sample size | High |
Broadfield et al. [16] | Experimental Study | N/A | Moderate | Low | Relevance to oral cancer | Moderate |
He et al. [104] | In vitro and in vivo | N/A | Moderate | Low | Preclinical relevance | Moderate |
Item | Content |
---|---|
Applications of Metformin | Treatment of T2DM [19], oral cancer (especially OSCC) [11], cardiovascular and renal protection [23,31,33], PCOS [34], and other cancers (breast cancer [42], colorectal cancer [16], etc.) |
Main Mechanisms of Action | |
Advantages | |
Challenges |
|
Clinical Studies and Evidence |
|
Future Research Directions |
|
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© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
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Li, J.-H.; Hsin, P.-Y.; Hsiao, Y.-C.; Chen, B.-J.; Zhuang, Z.-Y.; Lee, C.-W.; Lee, W.-J.; Vo, T.T.T.; Tseng, C.-F.; Tseng, S.-F.; et al. A Narrative Review: Repurposing Metformin as a Potential Therapeutic Agent for Oral Cancer. Cancers 2024, 16, 3017. https://doi.org/10.3390/cancers16173017
Li J-H, Hsin P-Y, Hsiao Y-C, Chen B-J, Zhuang Z-Y, Lee C-W, Lee W-J, Vo TTT, Tseng C-F, Tseng S-F, et al. A Narrative Review: Repurposing Metformin as a Potential Therapeutic Agent for Oral Cancer. Cancers. 2024; 16(17):3017. https://doi.org/10.3390/cancers16173017
Chicago/Turabian StyleLi, Jui-Hsiang, Pei-Yi Hsin, Yung-Chia Hsiao, Bo-Jun Chen, Zhi-Yun Zhuang, Chiang-Wen Lee, Wei-Ju Lee, Thi Thuy Tien Vo, Chien-Fu Tseng, Shih-Fen Tseng, and et al. 2024. "A Narrative Review: Repurposing Metformin as a Potential Therapeutic Agent for Oral Cancer" Cancers 16, no. 17: 3017. https://doi.org/10.3390/cancers16173017