The molecular mechanisms of ferroptosis and its role in glioma progression and treatment Mengyang Lu 1,2† , Yuanshuai Zhou 2† , Linjuan Sun 2,3 , Shaheryar Shafi 2,3 , Nafees Ahmad 4 , Minxuan Sun 2 * and Jun Dong 5 * 1 Noncoding RNA and Cancer Lab, Faculty of Life Sciences, Shanghai University, Shanghai, China, 2 Jiangsu Key Laboratory of Medical Optics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, China, 3 School of Biomedical Engineering, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China, 4 Institute of Biomedical and Genetic Engineering, Islamabad, Pakistan, 5 Department of Neurosurgery, The Second Affiliated Hospital of Soochow University, Suzhou, China Ferroptosis is one of the programmed modes of cell death that has attracted widespread attention recently and is capable of influencing the developmental course and prognosis of many tumors. Glioma is one of the most common primary tumors of the central nervous system, but effective treatment options are very limited. Ferroptosis plays a critical role in the glioma progression, affecting tumor cell proliferation, angiogenesis, tumor necrosis, and shaping the immune-resistant tumor microenvironment. Inducing ferroptosis has emerged as an attractive strategy for glioma. In this paper, we review ferroptosis-related researches on glioma progression and treatment. KEYWORDS ferroptosis, molecular mechanism, role, glioma progression, combination therapy Introduction Ferroptosis is an iron-dependent form of programmed cell death, is more immunogenic than apoptosis. During ferroptosis, the level of reactive oxygen species (ROS) increases and induces lipid peroxidation (LPO) (1, 2). Ferroptosis is widely present in the development of many cancers, such as liver cancer, gastric cancer, lung cancer, colorectal cancer, ovarian cancer, breast cancer, glioma, and hematologic tumors (3). Ferroptosis has attracted increasing attention since its naming in 2012 (4). The process of ferroptosis involves multiple signaling pathways and regulatory mechanisms that interact with other cell death modalities in the development of glioma (3, 5–7). It has been shown that increased ROS during ferroptosis can initiate LPO by interacting with polyunsaturated fatty acids in lipid membranes, thereby mediating chemoresistance in gliomas (8). A deeper understanding of the mechanism Frontiers in Oncology frontiersin.org 01 OPEN ACCESS EDITED BY Eduard Yakubov, Paracelsus Medical Private University, Germany REVIEWED BY Daishi Chen, Shenzhen People’s Hospital, Jinan University, China Wenchao Gu, University of Tsukuba, Japan *CORRESPONDENCE Minxuan Sun minxuan.sun@sibet.ac.cn Jun Dong dongjun@suda.edu.cn † These authors have contributed equally to this work and share first authorship SPECIALTY SECTION This article was submitted to Neuro-Oncology and Neurosurgical Oncology, a section of the journal Frontiers in Oncology RECEIVED 11 April 2022 ACCEPTED 05 July 2022 PUBLISHED 16 August 2022 CITATION Lu M, Zhou Y, Sun L, Shafi S, Ahmad N, Sun M and Dong J (2022) The molecular mechanisms of ferroptosis and its role in glioma progression and treatment. Front. Oncol. 12:917537. doi: 10.3389/fonc.2022.917537 COPYRIGHT © 2022 Lu, Zhou, Sun, Shafi, Ahmad, Sun and Dong. 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) and the copyright owner(s) 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. TYPE Review PUBLISHED 16 August 2022 DOI 10.3389/fonc.2022.917537