{"doi":"10.3390/cells13030219","title":"EZH2 Inhibition Sensitizes IDH1R132H-Mutant Gliomas to Histone Deacetylase Inhibitor","abstract":"Isocitrate Dehydrogenase-1 (IDH1) is commonly mutated in lower-grade diffuse gliomas. The IDH1R132H mutation is an important diagnostic tool for tumor diagnosis and prognosis; however, its role in glioma development, and its impact on response to therapy, is not fully understood. We developed a murine model of proneural IDH1R132H-mutated glioma that shows elevated production of 2-hydroxyglutarate (2-HG) and increased trimethylation of lysine residue K27 on histone H3 (H3K27me3) compared to IDH1 wild-type tumors. We found that using Tazemetostat to inhibit the methyltransferase for H3K27, Enhancer of Zeste 2 (EZH2), reduced H3K27me3 levels and increased acetylation on H3K27. We also found that, although the histone deacetylase inhibitor (HDACi) Panobinostat was less cytotoxic in IDH1R132H-mutated cells (either isolated from murine glioma or oligodendrocyte progenitor cells infected in vitro with a retrovirus expressing IDH1R132H) compared to IDH1-wild-type cells, combination treatment with Tazemetostat is synergistic in both mutant and wild-type models. These findings indicate a novel therapeutic strategy for IDH1-mutated gliomas that targets the specific epigenetic alteration in these tumors.","journal":"Cells","year":2024,"id":453257,"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":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9591,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":633211,"name":"Franklin Garcia","orcid":"0000-0002-3949-9633","position":1,"is_corresponding":false},{"id":245158,"name":"Angeliki Mela","orcid":"0000-0003-0099-9267","position":2,"is_corresponding":false},{"id":1276175,"name":"Liang Lei","orcid":null,"position":3,"is_corresponding":false},{"id":107942,"name":"Pavan S. Upadhyayula","orcid":"0000-0003-2071-6965","position":4,"is_corresponding":false},{"id":245159,"name":"Aayushi Mahajan","orcid":"0000-0003-3966-2936","position":5,"is_corresponding":false},{"id":248227,"name":"Nelson Humala","orcid":null,"position":6,"is_corresponding":false},{"id":1276176,"name":"Lisa Manier","orcid":null,"position":7,"is_corresponding":false},{"id":232779,"name":"Richard M. Caprioli","orcid":"0000-0001-5859-3310","position":8,"is_corresponding":false},{"id":278684,"name":"Alfredo Quiñones‐Hinojosa","orcid":"0000-0003-4262-5968","position":9,"is_corresponding":false},{"id":331549,"name":"Patrizia Casaccia","orcid":"0000-0002-4785-9264","position":10,"is_corresponding":false},{"id":107943,"name":"Peter Canoll","orcid":"0000-0002-7001-0226","position":11,"is_corresponding":false},{"id":512052,"name":"Lisa Sprinzen","orcid":"0000-0002-4885-4940","position":0,"is_corresponding":true}],"reference_count":61,"raw_metadata":null,"created_at":"2026-07-19T02:02:58.784290Z","pmid":"38334611","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":[]}