{"doi":"10.1093/noajnl/vdaf066","title":"Repurposing the anthelmintic drug mebendazole in combination with radiation therapy in an isocitrate dehydrogenase mutant glioma model","abstract":"Background: Heterozygous point somatic mutation in isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) are the most common genetic alterations in malignant glioma. This diffusely infiltrating glioma frequently progresses, despite maximal resection, radiation therapy (RT), and sometimes chemotherapy. We previously identified a brain-penetrant anthelminthic drug, Mebendazole, as a potential repurposed therapy for malignant glioma. Here, we tested the effect of mebendazole in combination with ionizing RT, part of the standard care for high-grade malignant glioma, in an IDH-mutant model. Methods: This study utilized glioma cells from a patient with mutant IDH1, to test the effect of mebendazole in combination with radiation in vitro on cell proliferation, cell cycle, and the apoptosis pathway. An orthotopic IDH-mutant grade III malignant glioma model was employed for in vivo experiments. Results: Mebendazole, in nanomolar concentrations, reduced cell proliferation, increased caspase-dependent apoptosis, and increased the DNA damage marker, ɣH2AX. The combination of mebendazole with RT, further reduced cell growth, arrested cells in G2/M, and disrupted the cell cycle and DNA damage pathways. An IDH-mutant xenograft model subjected to mebendazole plus RT showed improved survival compared to either therapy alone. Conclusions: Mebendazole plus RT increased apoptosis and provided a survival benefit in the IDH-mutant mouse model, supporting future clinical testing.","journal":"Neuro-Oncology Advances","year":2025,"id":526081,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9521,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":327464,"name":"Marina da Costa Rosa","orcid":null,"position":1,"is_corresponding":false},{"id":65277,"name":"Gregory J. Riggins","orcid":"0000-0002-4538-0436","position":2,"is_corresponding":false},{"id":1257533,"name":"Alex Shimura Yamashita","orcid":"0000-0003-4998-0989","position":0,"is_corresponding":true}],"reference_count":34,"raw_metadata":null,"created_at":"2026-07-19T02:50:25.860105Z","pmid":"40568681","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}