Oncology Central

Potential therapeutic target discovered for diffuse intrinsic pontine glioma

Through studying the mechanisms underpinning the formation and growth of diffuse intrinsic pontine glioma (DIPG), a group of researchers from the University of Copenhagen (Denmark) may have identified a novel therapeutic target for its treatment. The study was published recently in Nature Medicine.

DIPG is a rare malignant cerebral tumour that primarily affects children. Approximately 80% of DIPGs harbor mutations located in the histone H3 genes, one of these mutations is termed H3K27M.

Lead author Kristian Helin from the University of Copenhagen commented: “DIPG is a terrible disease with very poor survival. Before we can identify a treatment, we need to understand the mechanisms underlying the formation and growth of the tumor. We have now made a major step forward and we also have ideas for possible treatment.”

Utilizing a mouse model of DIPG in which H3K27M potentiates tumorigenesis and primary patient-derived DIPG cell lines, the team were able to halt tumor cell growth by utilizing EZH2 inhibitors.

Helin explained: “We have identified a possible method for treating this type of tumor. We know of a substance that is being trialled right now for another type of tumor. This substance is a so-called inhibitor for the EZH2 protein. We have tested the inhibitor on the mouse models and on cell lines from human tissue samples and have seen efficacy in both. The next step will be to collect preclinical data so that we can make a start on clinical trials.”

The researchers have already established a collaboration with a biotech company which is currently testing the EZH2 inhibitor in a Phase II trial on B-cell lymphomas and by next year they hope to collect sufficient preclinical data to be able to begin clinical trials.

Mohammad F, Weissmann S, Leblanc B et al. EZH2 is a potential therapeutic target for H3K27M-mutant pediatric gliomas Nature Medicine doi:10.1038/nm.4293 (2017); University of Copenhagen press release http://healthsciences.ku.dk/news/2017/02/treatment-of-malignant-brain-tumour-in-children-gets-closer/




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