Computational repositioning and preclinical validation of mifepristone for human vestibular schwannoma

Sci Rep. 2018 Apr 3;8(1):5437. doi: 10.1038/s41598-018-23609-7.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Algorithms
  • Cell Line, Tumor
  • Drug Evaluation, Preclinical / methods*
  • Drug Repositioning / methods*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Mifepristone / pharmacology*
  • Neuroma, Acoustic / pathology*


  • Mifepristone