A new treatment approach for children with diffuse intrinsic pontine glioma

26 June 2014

Professor Chris Jones, The Institute of Cancer Research, London

Diffuse intrinsic pontine glioma is a childhood brain tumour that is almost universally fatal, with more than 90 per cent of children succumbing to their illness within 18 months of diagnosis.

This project is exploring the development of new treatment approaches targeting a newly-identified genetic mutation present in the tumour cells of some children with DIPG.

Amount of grant: £264,117 | Date of award: June 2014

Overview

Diffuse intrinsic pontine glioma (DIPG) is a devastating childhood cancer that few, if any, children survive. More than 90 per cent of children diagnosed with DIPG die within 18 months of diagnosis.

Professor Chris Jones and colleagues at the Institute of Cancer Research recently discovered that the tumour cells in around a quarter of DIPG patients have mutations in a gene known as ACVR1.

These mutations in ACVR1 have never been seen in any other form of cancer, but are the same as those found in every cell of the body in patients with a condition called fibrodysplasia ossificans progressiva (FOP). This is a debilitating condition where the soft tissue turns to bone during childhood. The link between FOP and DIPG has never been reported before and highlights the important overlap between processes which control normal tissue development and those which control cancer. The hope is that ACVR1 represents a new target for developing better treatments for children with DIPG.  

In this new project, the team will investigate whether treating DIPG cells with specific drugs designed to inhibit the action of ACVR1 will stop the cells growing. This will be done both in vitro, that is in laboratory culture dishes, and also in vivo, that is in mice. They have a collection of DIPG cells with and without the ACVR1 mutation to test in this way, and several potential new drugs. They will also use the ACVR1 mutated cells in a very large scale screening exercise to look for other ways in which to kill them. Finally, the team will also aim to breed mice with the mutated ACVR1 gene to help them better understand how the tumours develop and how better to treat them.

About the research team

This is an excellent proposal, developed by scientists who are leaders in brain cancer research.
External reviewer
Professor Chris Jones is one of the UK’s leading experts in childhood brain tumours and specifically in DIPG. His lab has been responsible for some of the key findings underpinning the realisation that paediatric high grade gliomas (HGG) and DIPG are different diseases, both from each other, and from similar-looking tumours occurring in adults.

Chris is Chair of the HGG/DIPG Biology committee of the SIOPE Brain Tumour Working Group and as such has a European leadership role in generating new treatment approaches for these diseases.

He is collaborating on this project with his colleague Dr Louis Chesler, also from ICR – a specialist in new drug development - and Dr Darren Hargrave, a paediatric oncologist from Great Ormond Street Hospital and a worldwide leader in taking forward findings such as these into clinical trial.

What difference will this project make?

By the end of this study, the team hopes to have produced sufficient data to justify, if promising, the opening of a clinical trial of new drugs inhibiting the mutant ACVR1 gene in DIPG.

As there is currently no effective treatment for children with this devastating disease, this project represents the most compelling new hope for some time.

Read more: About childhood brain tumoursOther brain tumour research | Patient stories: brain tumours

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