Sagers, JessicaBrown, Adam S.Vasilijic, SasaM. Lewis, RebeccaSahin, Mehmet I.Landegger, LukasPerlis, Roy H.Kohane, IsaacWelling, DuanePatel, ChiragStankovic, Konstantina2018-05-302018Sagers, J. E., A. S. Brown, S. Vasilijic, R. M. Lewis, M. I. Sahin, L. D. Landegger, R. H. Perlis, et al. 2018. “Computational repositioning and preclinical validation of mifepristone for human vestibular schwannoma.” Scientific Reports 8 (1): 5437. doi:10.1038/s41598-018-23609-7. http://dx.doi.org/10.1038/s41598-018-23609-7.http://nrs.harvard.edu/urn-3:HUL.InstRepos:37068178The 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.en-USJournal Article2018-05-3010.1038/s41598-018-23609-7