Pharmacologic inhibition of histone demethylation as a therapy for pediatric brainstem glioma
Menée sur des lignées cellulaires et à l'aide de xénogreffes, cette étude suggère l'intérêt d'une stratégie basée sur l'inhibition d'une déméthylase (JMJD3) pour le traitement des patients pédiatriques atteints d'un gliome du pont cérébral présentant la mutation K27M de l'histone H3.3
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.
Nature Medicine 2014