- Pharmacologic inhibition of histone demethylation as a therapy for pediatric brainstem glioma.
Pharmacologic inhibition of histone demethylation as a therapy for pediatric brainstem glioma.
Nature medicine (2014-11-18)
Rintaro Hashizume, Noemi Andor, Yuichiro Ihara, Robin Lerner, Haiyun Gan, Xiaoyue Chen, Dong Fang, Xi Huang, Maxwell W Tom, Vy Ngo, David Solomon, Sabine Mueller, Pamela L Paris, Zhiguo Zhang, Claudia Petritsch, Nalin Gupta, Todd A Waldman, C David James
PMID25401693
초록
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.