Pharmacologic inhibition of histone demethylation as a therapy for pediatric brainstem glioma
Nature medicine, 2014•nature.com
Pediatric brainstem gliomas often harbor oncogenic K27M mutation of histone H3. 3. Here
we show that GSKJ4 pharmacologic inhibition of K27 demethylase JMJD3 increases cellular
H3K27 methylation in K27M tumor cells and demonstrate potent antitumor activity both in
vitro against K27M cells and in vivo against K27M xenografts. Our results demonstrate that
increasing H3K27 methylation by inhibiting K27 demethylase is a valid therapeutic strategy
for treating K27M-expressing brainstem glioma.
we show that GSKJ4 pharmacologic inhibition of K27 demethylase JMJD3 increases cellular
H3K27 methylation in K27M tumor cells and demonstrate potent antitumor activity both in
vitro against K27M cells and in vivo against K27M xenografts. Our results demonstrate that
increasing H3K27 methylation by inhibiting K27 demethylase is a valid therapeutic strategy
for treating K27M-expressing brainstem glioma.
Abstract
Pediatric brainstem gliomas often harbor oncogenic K27M mutation of histone H3.3. Here we show that GSKJ4 pharmacologic inhibition of K27 demethylase JMJD3 increases cellular H3K27 methylation in K27M tumor cells and demonstrate potent antitumor activity both in vitro against K27M cells and in vivo against K27M xenografts. Our results demonstrate that increasing H3K27 methylation by inhibiting K27 demethylase is a valid therapeutic strategy for treating K27M-expressing brainstem glioma.
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