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Computational repositioning and preclinical validation of mifepristone for human
vestibular schwannoma
#MMPMID29615643
Sagers JE
; Brown AS
; Vasilijic S
; Lewis RM
; Sahin MI
; Landegger LD
; Perlis RH
; Kohane IS
; Welling DB
; Patel CJ
; Stankovic KM
Sci Rep
2018[Apr]; 8
(1
): 5437
PMID29615643
show ga
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.
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