Professor Chris Jones, The Institute of Cancer Research

The search for new treatments for the childhood brainstem tumour DIPG

Professor Chris Jones was awarded a Brain Research UK project grant in September 2018 for his research into the childhood brain tumour DIPG. 

DIPG develops in the brain stem, mainly presenting in children aged 5 to 10 years. There is no cure and most children die within 18 months of diagnosis. 

In this project, Professor Jones is building on previous work that has found that a gene called ACVR1 is mutated in some DIPG tumours. It is thought that finding a drug that targets this mutation could be an effective way to treat DIPG, and we hope that this project will lead into a clinical trial of new drugs. 

Following rigorous assessment as part of our competitive project grant round, this project was selected for funding because the members of our Scientific Advisory Panel felt that it would make an important contribution to knowledge in an important area, with high unmet need. Whilst acknowledging the rarity of DIPG, the Panel emphasised its devastating impact. Professor Jones is building on a solid body of previous work that has advanced our understanding of DIPG, and is very well-placed to succeed in his aims of delivering an effective treatment for DIPG. 

About DIPG

Diffuse intrinsic pontine glioma (DIPG) is a high grade childhood brain tumour. It is the second most common primary high grade brain tumour in children, affecting 20 to 30 children a year in the UK. It has no cure. 

DIPG develops in a part of the brain stem known as the pons, which controls essential bodily functions including heartbeat, breathing, swallowing, eyesight and balance. 

The pons is inaccessible surgically. Chemotherapy is ineffective. Radiotherapy can temporarily slow the tumour's growth but is not curative. Ninety per cent of children die within 18 months of diagnosis, and survival beyond two years is almost unheard of. 

Effective treatments are desperately needed. 

The search for new treatments for DIPG

Professor Chris Jones is focused on the genetics of childhood brain tumours, especially DIPG. His aim is to find the genes that are driving the development of these tumours, and to find ways to translate his team's discoveries into new treatments for young patients. 

His team was part of an international collaborative effort to sequence the genome of DIPG, in work that was published in 2014. One of their most notable findings was a mutation in a gene called ACVR1, a mutation not seen in any other type of cancer. The same mutation is, however, found in a disease known as stone man syndrome, a debilitating genetic condition in which muscles can turn to bone. The unexpected discovery, linking these two drastically different diseases, meant that research into drugs to treat stone man syndrome might also be important in the search for treatments for DIPG. 

Prof Jones has developed a thorough understanding of the role of ACVR1 in the biology of DIPG and believes that finding a drug that can target the mutation could represent an effective treatment for DIPG. 

This new project, funded by Brain Research UK in collaboration with the DIPG Collaborative, builds on previous work showing that drugs that inhibit ACVR1 can modestly prolong survival in mice with human DIPG tumours. The team's next step is to see if they can enhance the effect using combinations of different drugs. The key is to find the right combination at the right dose. They also need to assess the interaction of candidate drugs with radiotherapy, as this is the current standard of care in DIPG. 

An important step on the pathway to human trial is the development of a mouse model of DIPG, which they can use for advanced testing of potential therapies. Existing models involve grafting a tumour onto a mouse whose immune system has been disabled - a so-called xenograft. This is useful, and the best option currently available. 

However, a genetically engineered mouse model is more representative of a real tumour. It will enable the collection of important evidence about the safety and effectiveness of potential new therapies in a living system with a fully functioning immune system, as well as giving further insights into the role of ACVR1 in the development of DIPG. 

“The team’s development of novel animal models provides a unique opportunity to be able to robustly test novel agents and develop effective therapies. The lack of these animal models in previous years has seriously hampered previous research efforts and has led to the failure of multiple previous clinical trials.” External reviewer.


DIPG is a rare but devastating childhood brain tumour

There is no effective treatment, meaning that it is considered fatal from the outset. 

In the last five years, thanks to advances in genetic sequencing technology, new biological discoveries and worldwide collaborative research efforts, there is a glimmer of hope. Effective treatments may be within reach.

Professor Chris Jones is one of the world’s leading researchers in the field of DIPG. He has excellent collaborations, both internally at the Institute of Cancer Research, nationally, and internationally – especially important when working in such a rare tumour type.

Professor Jones has played a key role in the progress made to date, and in this project he continues to drive this progress. The expectation is that – by the end of this project – he will have identified new therapies, tested in valid animal models, ready for translation through to clinical trial in young patients.

“The applicant has laid out a well thought out, realistic and innovative proposal that has a real prospect of identifying an effective therapy for DIPG.” External reviewer.

Related research projects

Research into brain tumours is one of our current priority research areas, reflecting the large unmet need in this area. Our aim is to fund projects that will help us to understand the causes and underlying mechanisms of brain tumours, and help us to diagnose and treat them more effectively. 

Other projects currently funded under this theme include: