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Emerging evidence indicates that AEDs possess direct antitumor activity independent of their antiepileptic effects, highlighting a promising novel direction for CNS tumor therapy. This review elucidates the multifaceted antitumor mechanisms of classic (e.g., valproic acid and levetiracetam) and novel (e.g., cannabidiol) AEDs, including their impacts on metabolic reprogramming, epigenetic regulation, endoplasmic reticulum stress and unfolded protein response (ERS-UPR), ion homeostasis, and the tumor immune microenvironment (TIME) to provide new insights and a theoretical basis for developing multitarget therapeutic strategies.<\/jats:p>","DOI":"10.3390\/cells15050409","type":"journal-article","created":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T14:51:29Z","timestamp":1772117489000},"page":"409","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Beyond Epilepsy Control: Repurposing Antiepileptic Drugs in Central Nervous System Tumor Therapy"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-9829-3900","authenticated-orcid":false,"given":"Haochen","family":"Zhao","sequence":"first","affiliation":[{"name":"Sino-German Neuro-Oncology Molecular Laboratory, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"},{"name":"Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"},{"name":"Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Jiang","sequence":"additional","affiliation":[{"name":"Sino-German Neuro-Oncology Molecular Laboratory, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"},{"name":"Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"},{"name":"Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quanji","family":"Wang","sequence":"additional","affiliation":[{"name":"Sino-German Neuro-Oncology Molecular Laboratory, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"},{"name":"Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"},{"name":"Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zihan","family":"Wang","sequence":"additional","affiliation":[{"name":"Sino-German Neuro-Oncology Molecular Laboratory, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"},{"name":"Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"},{"name":"Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yimin","family":"Huang","sequence":"additional","affiliation":[{"name":"Sino-German Neuro-Oncology Molecular Laboratory, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"},{"name":"Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"},{"name":"Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3241-7567","authenticated-orcid":false,"given":"Ting","family":"Lei","sequence":"additional","affiliation":[{"name":"Sino-German Neuro-Oncology Molecular Laboratory, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"},{"name":"Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"},{"name":"Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"23","DOI":"10.3892\/ijmm.2025.5523","article-title":"Seizures in brain tumors: Pathogenesis, risk factors and management (Review)","volume":"55","author":"Dantio","year":"2025","journal-title":"Int. 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