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REVIEW article

Front. Oncol.
Sec. Pharmacology of Anti-Cancer Drugs
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1482050
This article is part of the Research Topic Innovative Approaches in Glioma Therapy: Exploring New Therapeutic Frontiers View all articles

Advances in the treatment of glioma-related signaling pathways and mechanisms by metformin

Provisionally accepted
Xingyuan Ma Xingyuan Ma 1Chao Sun Chao Sun 2Xiao Ding Xiao Ding 3Yuhang Zhang Yuhang Zhang 1Tingzhen Deng Tingzhen Deng 1Yatao Wang Yatao Wang 1Haijun Yang Haijun Yang 1Ruiwen Ding Ruiwen Ding 1Haotian Li Haotian Li 1Dawen Wang Dawen Wang 1Maohua Zheng Maohua Zheng 4*
  • 1 The First School of Clinical Medicine, Lanzhou University, Lanzhou, China
  • 2 Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
  • 3 The third Department of Surgery, Armed Police Hospital of Tianjin, Tianjin, China
  • 4 First Hospital of Lanzhou University, Lanzhou, Gansu Province, China

The final, formatted version of the article will be published soon.

    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.

    Keywords: Metformin, Glioma, ferroptosis, Oxidative Stress, AMPK signaling pathway, Apoptosis, glioma immunity, CLIC1

    Received: 17 Aug 2024; Accepted: 06 Jan 2025.

    Copyright: © 2025 Ma, Sun, Ding, Zhang, Deng, Wang, Yang, Ding, Li, Wang and Zheng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Maohua Zheng, First Hospital of Lanzhou University, Lanzhou, Gansu Province, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.