Computational repositioning and preclinical validation of mifepristone for human vestibular schwannoma

Abstract The computational repositioning of existing drugs represents an appealing avenue for identifying effective compounds to treat diseases with no FDA-approved pharmacotherapies. Here we present the largest meta-analysis to date of differential gene expression in human vestibular schwannoma (VS...

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Autores principales:	Jessica E. Sagers, Adam S. Brown, Sasa Vasilijic, Rebecca M. Lewis, Mehmet I. Sahin, Lukas D. Landegger, Roy H. Perlis, Isaac S. Kohane, D. Bradley Welling, Chirag J. Patel, Konstantina M. Stankovic
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Vestibular Schwannoma Schwannoma Cells Mifepristone Treatment Randomized Block ANOVA Cytomics FC500 Flow Cytometer Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1ffccaa40027402cbbc35cab80f60447
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spelling	oai:doaj.org-article:1ffccaa40027402cbbc35cab80f604472021-12-02T15:05:30ZComputational repositioning and preclinical validation of mifepristone for human vestibular schwannoma10.1038/s41598-018-23609-72045-2322https://doaj.org/article/1ffccaa40027402cbbc35cab80f604472018-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-23609-7https://doaj.org/toc/2045-2322Abstract The computational repositioning of existing drugs represents an appealing avenue for identifying effective compounds to treat diseases with no FDA-approved pharmacotherapies. Here we present the largest meta-analysis to date of differential gene expression in human vestibular schwannoma (VS), a debilitating intracranial tumor, and use these data to inform the first application of algorithm-based drug repositioning for this tumor class. We apply an open-source computational drug repositioning platform to gene expression data from 80 patient tumors and identify eight promising FDA-approved drugs with potential for repurposing in VS. Of these eight, mifepristone, a progesterone and glucocorticoid receptor antagonist, consistently and adversely affects the morphology, metabolic activity, and proliferation of primary human VS cells and HEI-193 human schwannoma cells. Mifepristone treatment reduces VS cell viability more significantly than cells derived from patient meningiomas, while healthy human Schwann cells remain unaffected. Our data recommend a Phase II clinical trial of mifepristone in VS.Jessica E. SagersAdam S. BrownSasa VasilijicRebecca M. LewisMehmet I. SahinLukas D. LandeggerRoy H. PerlisIsaac S. KohaneD. Bradley WellingChirag J. PatelKonstantina M. StankovicNature PortfolioarticleVestibular SchwannomaSchwannoma CellsMifepristone TreatmentRandomized Block ANOVACytomics FC500 Flow CytometerMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-12 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Vestibular Schwannoma Schwannoma Cells Mifepristone Treatment Randomized Block ANOVA Cytomics FC500 Flow Cytometer Medicine R Science Q
spellingShingle	Vestibular Schwannoma Schwannoma Cells Mifepristone Treatment Randomized Block ANOVA Cytomics FC500 Flow Cytometer Medicine R Science Q Jessica E. Sagers Adam S. Brown Sasa Vasilijic Rebecca M. Lewis Mehmet I. Sahin Lukas D. Landegger Roy H. Perlis Isaac S. Kohane D. Bradley Welling Chirag J. Patel Konstantina M. Stankovic Computational repositioning and preclinical validation of mifepristone for human vestibular schwannoma
description	Abstract The computational repositioning of existing drugs represents an appealing avenue for identifying effective compounds to treat diseases with no FDA-approved pharmacotherapies. Here we present the largest meta-analysis to date of differential gene expression in human vestibular schwannoma (VS), a debilitating intracranial tumor, and use these data to inform the first application of algorithm-based drug repositioning for this tumor class. We apply an open-source computational drug repositioning platform to gene expression data from 80 patient tumors and identify eight promising FDA-approved drugs with potential for repurposing in VS. Of these eight, mifepristone, a progesterone and glucocorticoid receptor antagonist, consistently and adversely affects the morphology, metabolic activity, and proliferation of primary human VS cells and HEI-193 human schwannoma cells. Mifepristone treatment reduces VS cell viability more significantly than cells derived from patient meningiomas, while healthy human Schwann cells remain unaffected. Our data recommend a Phase II clinical trial of mifepristone in VS.
format	article
author	Jessica E. Sagers Adam S. Brown Sasa Vasilijic Rebecca M. Lewis Mehmet I. Sahin Lukas D. Landegger Roy H. Perlis Isaac S. Kohane D. Bradley Welling Chirag J. Patel Konstantina M. Stankovic
author_facet	Jessica E. Sagers Adam S. Brown Sasa Vasilijic Rebecca M. Lewis Mehmet I. Sahin Lukas D. Landegger Roy H. Perlis Isaac S. Kohane D. Bradley Welling Chirag J. Patel Konstantina M. Stankovic
author_sort	Jessica E. Sagers
title	Computational repositioning and preclinical validation of mifepristone for human vestibular schwannoma
title_short	Computational repositioning and preclinical validation of mifepristone for human vestibular schwannoma
title_full	Computational repositioning and preclinical validation of mifepristone for human vestibular schwannoma
title_fullStr	Computational repositioning and preclinical validation of mifepristone for human vestibular schwannoma
title_full_unstemmed	Computational repositioning and preclinical validation of mifepristone for human vestibular schwannoma
title_sort	computational repositioning and preclinical validation of mifepristone for human vestibular schwannoma
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/1ffccaa40027402cbbc35cab80f60447
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Computational repositioning and preclinical validation of mifepristone for human vestibular schwannoma

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