Role and Mechanisms of Exercise Therapy in Enhancing Drug Treatment for Glioma: A Review

Guanghui Wu ^1,2* Yisheng Chen ^1,2,3* Chong Chen ⁴ Jianling Liu ³ Qiaowu Wu ³ Yazhen Zhang ⁵ Runqiong Chen ³ Jianzhong Xiao ³ Yusheng Su ³ Haojun Shi ⁶ Chunsheng Yu ³ Miao Wang ³ Yifan Ouyang ³ Airong Jiang ³ Zhengzhou Chen ³ Xiao Ye ³ Chengwan Shen ³ Xianjun Li ³ Aikebaier Reheman ³ Ming Liu ^1,2* Jiancheng Shen ^1,2*

• ¹ Department of Neurosurgery, Ningde Municipal Hospital, Ningde Normal University, Ningde, China
• ² Department of Neurosurgery, Ningde Clinical Medical College, Fujian Medical University, Ningde, China
• ³ Fujian Key Laboratory of Toxicant and Drug Toxicology, Medical College, Ningde Normal University., Ningde, China
• ⁴ Chongqing Medical University, Chongqing, China
• ⁵ School of Physical Education, Ningde Normal University, Ningde, China
• ⁶ State Key Laboratory of Quality Research in Chinese Medicines, Macau University of Science and Technology, Macau, China

Gliomas, particularly glioblastoma (GBM), are among the most aggressive and challenging brain tumors to treat. Although current therapies such as chemotherapy, radiotherapy, and targeted treatments have extended patient survival to some extent, their efficacy remains limited and is often accompanied by severe side effects. In recent years, exercise therapy has gained increasing attention as an adjunctive treatment in clinical and research settings. Exercise not only improves patients' physical function and cognitive abilities but may also enhance the efficacy of conventional drug treatments by modulating the immune system, suppressing inflammatory responses, and improving blood-brain barrier permeability. This review summarizes the potential mechanisms of exercise in glioma treatment, including enhancing immune surveillance through activation of natural killer (NK) cells and T cells, and increasing drug penetration by improving blood-brain barrier function. Additionally, studies suggest that exercise can synergize with chemotherapy and immunotherapy, improving treatment outcomes while reducing drug-related side effects. Although the application of exercise therapy in glioma patients is still in the exploratory phase, existing evidence indicates its significant clinical value as an adjunctive approach, with the potential to become a new standard in glioma treatment in the future.