{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T03:56:48Z","timestamp":1791086208632,"version":"4.1.0"},"reference-count":37,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,5,4]],"date-time":"2023-05-04T00:00:00Z","timestamp":1683158400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U01 CA172027"],"award-info":[{"award-number":["U01 CA172027"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U01 CA264039"],"award-info":[{"award-number":["U01 CA264039"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["F31CA247564"],"award-info":[{"award-number":["F31CA247564"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"predoctoral fellowship","doi-asserted-by":"publisher","award":["U01 CA172027"],"award-info":[{"award-number":["U01 CA172027"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"predoctoral fellowship","doi-asserted-by":"publisher","award":["U01 CA264039"],"award-info":[{"award-number":["U01 CA264039"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"predoctoral fellowship","doi-asserted-by":"publisher","award":["F31CA247564"],"award-info":[{"award-number":["F31CA247564"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Tomography"],"abstract":"<jats:p>Histone deacetylase inhibitors (HDACis) are drugs that target the epigenetic state of cells by modifying the compaction of chromatin through effects on histone acetylation. Gliomas often harbor a mutation of isocitrate dehydrogenase (IDH) 1 or 2 that leads to changes in their epigenetic state presenting a hypermethylator phenotype. We postulated that glioma cells with IDH mutation, due to the presence of epigenetic changes, will show increased sensitivity to HDACis. This hypothesis was tested by expressing mutant IDH1 with a point alteration\u2014converting arginine 132 to histidine\u2014within glioma cell lines that contain wild-type IDH1. Glioma cells engineered to express mutant IDH1 produced D-2-hydroxyglutarate as expected. When assessed for response to the pan-HDACi drug belinostat, mutant IDH1-expressing glioma cells were subjected to more potent inhibition of growth than the corresponding control cells. Increased sensitivity to belinostat correlated with the increased induction of apoptosis. Finally, a phase I trial assessing the addition of belinostat to standard-of-care therapy for newly diagnosed glioblastoma patients included one patient with a mutant IDH1 tumor. This mutant IDH1 tumor appeared to display greater sensitivity to the addition of belinostat than the other cases with wild-type IDH tumors based on both standard magnetic resonance imaging (MRI) and advanced spectroscopic MRI criteria. These data together suggest that IDH mutation status within gliomas may serve as a biomarker of response to HDACis.<\/jats:p>","DOI":"10.3390\/tomography9030077","type":"journal-article","created":{"date-parts":[[2023,5,5]],"date-time":"2023-05-05T03:57:31Z","timestamp":1683259051000},"page":"942-954","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Mutant Isocitrate Dehydrogenase 1 Expression Enhances Response of Gliomas to the Histone Deacetylase Inhibitor Belinostat"],"prefix":"10.3390","volume":"9","author":[{"given":"Chi-Ming","family":"Chang","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, Emory University, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karthik K.","family":"Ramesh","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Emory University, Atlanta, GA 30322, USA"},{"name":"Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3029-4700","authenticated-orcid":false,"given":"Vicki","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Emory University, Atlanta, GA 30322, USA"},{"name":"Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3524-3726","authenticated-orcid":false,"given":"Saumya","family":"Gurbani","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Emory University, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2473-2305","authenticated-orcid":false,"given":"Lawrence R.","family":"Kleinberg","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Johns Hopkin University, Baltimore, MD 21287, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7992-1747","authenticated-orcid":false,"given":"Brent D.","family":"Weinberg","sequence":"additional","affiliation":[{"name":"Department of Radiology and Imaging Sciences, Emory University, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyunsuk","family":"Shim","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Emory University, Atlanta, GA 30322, USA"},{"name":"Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, GA 30322, USA"},{"name":"Department of Radiology and Imaging Sciences, Emory University, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui-Kuo G.","family":"Shu","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Emory University, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1807","DOI":"10.1126\/science.1164382","article-title":"An integrated genomic analysis of human glioblastoma multiforme","volume":"321","author":"Parsons","year":"2008","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1056\/NEJMoa0808710","article-title":"IDH1 and IDH2 mutations in gliomas","volume":"360","author":"Yan","year":"2009","journal-title":"N. 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