ArticleActa neuropathologica communications2026
Synergistic antitumor effect of temozolomide and perampanel in pediatric glioma: a case report and in vitro validation using patient-derived glioma sphere cells.
Article in Acta neuropathologica communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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Who cites it
1 citing paper in PubMed.
- Ion Channel-Targeting Modulators in Glioma: Pharmacological Advances and Therapeutic Perspectives.International journal of molecular sciences · 2026Review
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12 authors.
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Abstract
Pediatric low-grade gliomas are the most common central nervous system tumors; however, therapeutic options remain limited for tumors involving critical structures, such as the optic pathway, particularly when malignant transformation occurs. Temozolomide is widely used to treat high-grade gliomas; however, its clinical benefits in pediatric low-grade gliomas have been inconsistent. Recent laboratory studies have suggested that the antiepileptic drug perampanel, a selective noncompetitive antagonist of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptor, may enhance the antitumor activity of temozolomide; however, this has not been demonstrated in patients. To the best of our knowledge, this is the first clinical case in which a child with recurrent treatment-refractory optic pathway glioma with malignant transformation exhibited marked radiographic tumor regression following treatment with a combination of temozolomide and perampanel. This unexpected clinical response prompted further investigation using patient-derived glioma sphere cells generated from two independent glioma cases. In vitro analyses showed that perampanel suppressed cell proliferation and exhibited synergistic cytotoxicity when combined with temozolomide. Immunofluorescence analysis of the patient’s tumor tissue revealed high expression of GRIA1-4, a gene encoding the AMPA receptor subunit, particularly within CD44-positive glioma stem-like cells, supporting a mechanistic association between AMPA receptor signaling and treatment sensitivity. Complementary transcriptomic analysis using publicly available datasets showed that the elevated expression of GRIA family genes was associated with favorable survival in low-grade gliomas. Taken together, these findings suggest that perampanel potentiates the antitumor effects of temozolomide and highlight GRIA expression as a potential biomarker for AMPA receptor–targeted strategies in glioma.
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