Targeted inhibition of histone demethylase activity in brainstem glioma

Project: Research project

Project Details

Description

Diffuse intrinsic pontine gliomas (DIPGs) in children carry a very poor prognosis despite
the use of aggressive multi-modality treatment. No significant advances in the survival of
DIPG patients have been made over the last few decades, and new therapeutic
approaches are desperately needed. The lack of human DIPG tissue samples and a
limited understanding of the biology of these tumors, have prevented the identification of
effective therapeutic strategies. Recent genetic analysis revealed the presence of a
novel gene mutation in these tumors that alters a DNA binding protein, histone H3.3,
and our recently published work was the first to demonstrate that pharmacologic
inhibition of the histone modifying enzyme, JMJD3, increases cellular histone
methylation in mutant DIPG tumor cells, while demonstrating potent anti-tumor activity.
As such, JMJD3 appears to have oncogenic activity in contributing to the development
or maintenance of DIPG, the major goals of this project are to determine whether JMJD3
oncogenic activity is influenced by other histone-modifying enzymes, how other histone
modifying activities respond to sustained JMJD3 inhibition, and if JMJD3 inhibition can
be used to advantage, in treating DIPG, when combined with radiotherapy.
StatusFinished
Effective start/end date4/1/153/31/16

Funding

  • Bear Necessities Pediatric Cancer Foundation (Award Letter 6/25/15)

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