Advances in the treatment of glioma-related signaling pathways and mechanisms by metformin
Metformin (MET) is a commonly used drug for the treatment of type 2 diabetes in the department of endocrinology. In recent years, due to the few clinically effective treatment options including glioma, some scholars have proposed the possibility of metformin in the treatment of glioma, and studies h...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2025.1482050/full |
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| author | Xingyuan Ma Xingyuan Ma Chao Sun Xiao Ding Yuhang Zhang Yuhang Zhang Tingzhen Deng Tingzhen Deng Yatao Wang Yatao Wang Haijun Yang Haijun Yang Ruiwen Ding Ruiwen Ding Haotian Li Haotian Li Dawen Wang Dawen Wang Maohua Zheng Maohua Zheng |
| author_facet | Xingyuan Ma Xingyuan Ma Chao Sun Xiao Ding Yuhang Zhang Yuhang Zhang Tingzhen Deng Tingzhen Deng Yatao Wang Yatao Wang Haijun Yang Haijun Yang Ruiwen Ding Ruiwen Ding Haotian Li Haotian Li Dawen Wang Dawen Wang Maohua Zheng Maohua Zheng |
| author_sort | Xingyuan Ma |
| collection | DOAJ |
| description | Metformin (MET) is a commonly used drug for the treatment of type 2 diabetes in the department of endocrinology. In recent years, due to the few clinically effective treatment options including glioma, some scholars have proposed the possibility of metformin in the treatment of glioma, and studies have shown that metformin has a certain inhibitory effect on this tumor. This review explores the multiple mechanisms through which metformin exerts its antitumor effects, focusing on signaling pathways such as AMPK/mTOR, ferroptosis, autophagy, apoptosis and chloride ion channels (CLIC1). Metformin’s inhibition of glioma proliferation involves complex cellular processes, including mitochondrial dysfunction, increased reactive oxygen species (ROS) production, and modulation of immune responses. Additionally, metformin affects glioma stem cells by inhibiting key pathways, including STAT3, mTOR, and AKT, and altering the tumor microenvironment. While preclinical studies suggest that metformin enhances radiosensitivity and reduces tumor recurrence, its clinical application remains in early stages, with further studies needed to optimize dosing regimens and understand its full therapeutic potential. This review provides a comprehensive analysis of metformin’s molecular mechanisms in glioma treatment and highlights its potential as a novel therapeutic strategy, especially for treatment-resistant gliomas. |
| format | Article |
| id | doaj-art-4ca50ef7b36b4207becb2a06376cc41d |
| institution | Kabale University |
| issn | 2234-943X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj-art-4ca50ef7b36b4207becb2a06376cc41d2025-01-29T06:46:12ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-01-011510.3389/fonc.2025.14820501482050Advances in the treatment of glioma-related signaling pathways and mechanisms by metforminXingyuan Ma0Xingyuan Ma1Chao Sun2Xiao Ding3Yuhang Zhang4Yuhang Zhang5Tingzhen Deng6Tingzhen Deng7Yatao Wang8Yatao Wang9Haijun Yang10Haijun Yang11Ruiwen Ding12Ruiwen Ding13Haotian Li14Haotian Li15Dawen Wang16Dawen Wang17Maohua Zheng18Maohua Zheng19The First School of Clinical Medicine, Lanzhou University, Lanzhou, ChinaDepartment of Neurosurgery, The First Hospital of Lanzhou University, Lanzhou, ChinaDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, ChinaThe third Department of Surgery, Armed Police Hospital of Tianjin, Tianjin, ChinaThe First School of Clinical Medicine, Lanzhou University, Lanzhou, ChinaDepartment of Neurosurgery, The First Hospital of Lanzhou University, Lanzhou, ChinaThe First School of Clinical Medicine, Lanzhou University, Lanzhou, ChinaDepartment of Neurosurgery, The First Hospital of Lanzhou University, Lanzhou, ChinaThe First School of Clinical Medicine, Lanzhou University, Lanzhou, ChinaDepartment of Neurosurgery, The First Hospital of Lanzhou University, Lanzhou, ChinaThe First School of Clinical Medicine, Lanzhou University, Lanzhou, ChinaDepartment of Neurosurgery, The First Hospital of Lanzhou University, Lanzhou, ChinaThe First School of Clinical Medicine, Lanzhou University, Lanzhou, ChinaDepartment of Neurosurgery, The First Hospital of Lanzhou University, Lanzhou, ChinaThe First School of Clinical Medicine, Lanzhou University, Lanzhou, ChinaDepartment of Neurosurgery, The First Hospital of Lanzhou University, Lanzhou, ChinaThe First School of Clinical Medicine, Lanzhou University, Lanzhou, ChinaDepartment of Neurosurgery, The First Hospital of Lanzhou University, Lanzhou, ChinaThe First School of Clinical Medicine, Lanzhou University, Lanzhou, ChinaDepartment of Neurosurgery, The First Hospital of Lanzhou University, Lanzhou, ChinaMetformin (MET) is a commonly used drug for the treatment of type 2 diabetes in the department of endocrinology. In recent years, due to the few clinically effective treatment options including glioma, some scholars have proposed the possibility of metformin in the treatment of glioma, and studies have shown that metformin has a certain inhibitory effect on this tumor. This review explores the multiple mechanisms through which metformin exerts its antitumor effects, focusing on signaling pathways such as AMPK/mTOR, ferroptosis, autophagy, apoptosis and chloride ion channels (CLIC1). Metformin’s inhibition of glioma proliferation involves complex cellular processes, including mitochondrial dysfunction, increased reactive oxygen species (ROS) production, and modulation of immune responses. Additionally, metformin affects glioma stem cells by inhibiting key pathways, including STAT3, mTOR, and AKT, and altering the tumor microenvironment. While preclinical studies suggest that metformin enhances radiosensitivity and reduces tumor recurrence, its clinical application remains in early stages, with further studies needed to optimize dosing regimens and understand its full therapeutic potential. This review provides a comprehensive analysis of metformin’s molecular mechanisms in glioma treatment and highlights its potential as a novel therapeutic strategy, especially for treatment-resistant gliomas.https://www.frontiersin.org/articles/10.3389/fonc.2025.1482050/fullmetformingliomaferroptosisoxidative stressAMPK signaling pathwayapoptosis |
| spellingShingle | Xingyuan Ma Xingyuan Ma Chao Sun Xiao Ding Yuhang Zhang Yuhang Zhang Tingzhen Deng Tingzhen Deng Yatao Wang Yatao Wang Haijun Yang Haijun Yang Ruiwen Ding Ruiwen Ding Haotian Li Haotian Li Dawen Wang Dawen Wang Maohua Zheng Maohua Zheng Advances in the treatment of glioma-related signaling pathways and mechanisms by metformin Frontiers in Oncology metformin glioma ferroptosis oxidative stress AMPK signaling pathway apoptosis |
| title | Advances in the treatment of glioma-related signaling pathways and mechanisms by metformin |
| title_full | Advances in the treatment of glioma-related signaling pathways and mechanisms by metformin |
| title_fullStr | Advances in the treatment of glioma-related signaling pathways and mechanisms by metformin |
| title_full_unstemmed | Advances in the treatment of glioma-related signaling pathways and mechanisms by metformin |
| title_short | Advances in the treatment of glioma-related signaling pathways and mechanisms by metformin |
| title_sort | advances in the treatment of glioma related signaling pathways and mechanisms by metformin |
| topic | metformin glioma ferroptosis oxidative stress AMPK signaling pathway apoptosis |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2025.1482050/full |
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