{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T16:00:21Z","timestamp":1787241621533,"version":"build-2736575974"},"reference-count":52,"publisher":"Oxford University Press (OUP)","issue":"1","funder":[{"DOI":"10.13039\/100018896","name":"Sylvester Comprehensive Cancer Center","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100018896","id-type":"DOI","asserted-by":"publisher"}]},{"name":"FCBTR"},{"DOI":"10.13039\/100018795","name":"FACCA","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100018795","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R25NS108937-01"],"award-info":[{"award-number":["R25NS108937-01"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Poor prognosis of glioblastoma patients and the extensive heterogeneity of glioblastoma at both the molecular and cellular level necessitates developing novel individualized treatment modalities via genomics-driven approaches.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study leverages numerous pharmacogenomic and tissue databases to examine drug repositioning for glioblastoma. RNA-seq of glioblastoma tumor samples from The Cancer Genome Atlas (TCGA, n = 117) were compared to \u201cnormal\u201d frontal lobe samples from Genotype-Tissue Expression Portal (GTEX, n = 120) to find differentially expressed genes (DEGs). Using compound gene expression data and drug activity data from the Library of Integrated Network-Based Cellular Signatures (LINCS, n = 66,512 compounds) CCLE (71 glioma cell lines), and Chemical European Molecular Biology Laboratory (ChEMBL) platforms, we employed a summarized reversal gene expression metric (sRGES) to \u201creverse\u201d the resultant disease signature for GBM and its subtypes. A multiparametric strategy was employed to stratify compounds capable of blood-brain barrier penetrance with a favorable pharmacokinetic profile (CNS-MPO).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Significant correlations were identified between sRGES and drug efficacy in GBM cell lines in both ChEMBL(r = 0.37, P &amp;lt; .001) and Cancer Therapeutic Response Portal (CTRP) databases (r = 0.35, P &amp;lt; 0.001). Our multiparametric algorithm identified two classes of drugs with highest sRGES and CNS-MPO: HDAC inhibitors (vorinostat and entinostat) and topoisomerase inhibitors suitable for drug repurposing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our studies suggest that reversal of glioblastoma disease signature correlates with drug potency for various GBM subtypes. This multiparametric approach may set the foundation for an early-phase personalized -omics clinical trial for glioblastoma by effectively identifying drugs that are capable of reversing the disease signature and have favorable pharmacokinetic and safety profiles.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/noajnl\/vdab192","type":"journal-article","created":{"date-parts":[[2021,12,31]],"date-time":"2021-12-31T11:54:37Z","timestamp":1640951677000},"source":"Crossref","is-referenced-by-count":7,"title":["A multiparametric pharmacogenomic strategy for drug repositioning predicts therapeutic efficacy for glioblastoma cell lines"],"prefix":"10.1093","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0183-1274","authenticated-orcid":false,"given":"Ashish H","family":"Shah","sequence":"first","affiliation":[{"name":"Department of Neurological Surgery, Sylvester Comprehensive Cancer Center, Miami, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Suter","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, Sylvester Comprehensive Cancer Center, Miami, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavan","family":"Gudoor","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, Sylvester Comprehensive Cancer Center, Miami, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tara T","family":"Doucet-O\u2019Hare","sequence":"additional","affiliation":[{"name":"Neuro-Oncology Branch, National Cancer Institute, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasileios","family":"Stathias","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Pharmacology, University of Miami, Miami, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5808-453X","authenticated-orcid":false,"given":"Iahn","family":"Cajigas","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, Sylvester Comprehensive Cancer Center, Miami, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Macarena","family":"de la Fuente","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Miami Miller School of Medicine, Miami, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vaidya","family":"Govindarajan","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, Sylvester Comprehensive Cancer Center, Miami, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexis A","family":"Morell","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, Sylvester Comprehensive Cancer Center, Miami, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel G","family":"Eichberg","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, Sylvester Comprehensive Cancer Center, Miami, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9164-4984","authenticated-orcid":false,"given":"Evan","family":"Luther","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, Sylvester Comprehensive Cancer Center, Miami, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor M","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, Sylvester Comprehensive Cancer Center, Miami, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Heiss","sequence":"additional","affiliation":[{"name":"Surgical Neurology Division, NINDS National Institute of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6631-7551","authenticated-orcid":false,"given":"Ricardo J","family":"Komotar","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, Sylvester Comprehensive Cancer Center, Miami, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4798-4989","authenticated-orcid":false,"given":"Michael E","family":"Ivan","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, Sylvester Comprehensive Cancer Center, Miami, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Schurer","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, Sylvester Comprehensive Cancer Center, Miami, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark 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