Drug target discovered for aggressive childhood brain tumour

In collaboration with the Press Association

US scientists have successfully used an experimental drug to prolong the lives of mice with an aggressive form of childhood brain cancer.

"Further studies will be needed to develop this into a new treatment for the children who desperately it” - Dr Chris Jones, Cancer Research UK

The disease, known as diffuse intrinsic pontine glioma (DIPG), is particularly hard to treat as tumours form in the brainstem – a region of the brain vital to controlling essential body functions such as breathing and heartbeat.

The location of these tumours makes them inoperable, and radio- and chemotherapy are also largely ineffective.

DIPG is also very rare, with around 20-30 children affected each year in the UK. This leaves experts with a small number of samples to study, making the hunt for new treatments a real challenge.

In the latest study, published in Nature Medicine, scientists at Northwestern University in the US have discovered a potential way of targeting a gene fault that has been found in most patients with the disease.

Commenting on the US team’s findings, Dr Chris Jones, a Cancer Research UK expert in childhood brain tumours from the Institute of Cancer Research in London, said: “The researchers have taken advantage of the unique biology of these tumour cells and suggested a way to overcome a specific internal 're-wiring' seen in the cells of most DIPG patients.”

This ‘re-wiring’ is a fault found in the H3F3A gene, which produces a type of protein called a histone, and has an important role in the development of DIPG.

Histones are protein molecules within each cell that act like spools for DNA to wrap around inside the nucleus.

Crucially, the fault in the H3F3A gene prevents the resulting protein from undergoing a chemical tagging process called ‘methylation’, which can control how genes are switched on or off.

Study leader Dr Rintaro Hashizume proposed that restoring methylation might offer a way to slow tumour growth and progression.

To test this the team worked with mice carrying tumours formed from DIPG cells. And they treated the mice with a drug that had previously been found to increase methylation when treating immune disorders.

The results showed that mice given the experimental drug – called GSKJ4 – for 10 days survived significantly longer than those that did not receive GSKJ4.

Dr Hashizume said: "We are so excited by these findings.

“We’ve identified a compound that may be useful for treating DIPG patients with this mutation."

While Jones agreed that new treatments for the disease were sorely needed, he stressed that the research was still at an early stage.

“Finding new ways to treat DIPG is one of the most difficult challenges in oncology. And these findings could lead to new drugs being developed in the future,” he said.

“But so far the results have only been shown in experiments in the laboratory, and many obstacles remain. Further studies will be needed to develop this into a new treatment for the children who desperately it.”


  • Hashizume, R, et al. (2014). Pharmacologic inhibition of histone demethylation as a therapy for pediatric brainstem glioma Nature Medicine DOI: 10.1038/nm.3716