Zebrafish Models in Glioma Research: Advances in Methodologies, Mechanistic Insights, and Therapeutic Frontiers

Runchao Tao¹Junying Qu¹Jing Zhao¹Baihui Wu¹Huaibiao Xu¹Liangwei Yang²Hongru Qin²Rongbing Chen³Qinsi Yang⁴Yongwei Cheng⁵Wei Wu⁶Da Sun^1*Min Cao⁷

• ¹Institute of Life Sciences & Biomedical Collaborative Innovation Center of Zhejiang Province, Wenzhou University, Wenzhou, China
• ²The First School of Medicine, School of Information and Engineering, Wenzhou Medical University, Wenzhou, Zhejiang Province, China
• ³Department of Biomedical Engineering, City University of Hong Kong, Kowloon, Hong Kong, SAR China
• ⁴Wenzhou Institute, University of Chinese Academy of Sciences, Beijing, Beijing, China
• ⁵National Engineering Research Center of Cell Growth Factor Drugs and Protein Biologics, Wenzhou Medical University, Wenzhou, Zhejiang Province, China
• ⁶Key Laboratory for Biorheological Science and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College of Chongqing University, Chongqing University, Chongqing, China
• ⁷The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou City People's Hospital, Quzhou, China

Glioma is the most common primary malignant brain tumor, which faces great challenges in clinical treatment due to its high invasiveness and resistance to existing treatments. In recent years, the zebrafish model has gradually become an important tool for glioma research due to its advantages such as easy genetic manipulation, strong optical transparency, and suitability for high-throughput imaging and drug screening. This article systematically reviews the three main strategies for zebrafish glioma modeling -chemical mutagenesis, genetic engineering and xenotransplantation, and describes their research applications in tumorigenesis, invasion process and treatment response. At the same time, this article deeply analyzes the limitations of the zebrafish model in terms of temperature differences, delayed development of the blood-brain barrier and immature immune system, and introduces the cutting-edge progress in recent years in the fields of CRISPR-mediated immune regulation, construction of high-temperature resistant strains and development of humanized models. Through a comprehensive review of current research applications, key challenges and future development directions, this article emphasizes the potential value of the zebrafish model as an important supplement to the mammalian model in exploring the immune mechanism of glioma and developing innovative treatment strategies.