Pharmacologic inhibition of histone demethylation as a therapy for pediatric brainstem glioma
2014; Nature Portfolio; Volume: 20; Issue: 12 Linguagem: Inglês
10.1038/nm.3716
ISSN1546-170X
AutoresRintaro Hashizume, Noemi Andor, Yuichiro Ihara, Robin G. Lerner, Haiyun Gan, Xiaoyue Chen, Fang Dong, Xi Huang, Maxwell W. Tom, Vy Ngo, David A. Solomon, Sabine Mueller, Pamela L. Paris, Zhiguo Zhang, Claudia Petritsch, Nalin Gupta, Todd Waldman, C. David James,
Tópico(s)Glioma Diagnosis and Treatment
ResumoHashizume et al. report a new therapeutic strategy for treating pediatric gliomas with mutations in the H3F3A gene by inhibiting histone demethylation. 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.
Referência(s)