Understanding treatment-resistance and disease-spread in childhood gliomas

10 October 2016

Professor Chris Jones, The Institute of Cancer Research

Paediatric glioblastoma and diffuse intrinsic pontine glioma are two of the most terrible forms of brain tumour to affect children, both incurable using existing treatments. The aim of this project is to advance understanding of how these tumours resist treatment and spread through the brain. This ultimately leads to the possibility of identifying new drugs that will improve the outcome for young patients with these tumours.

Amount of grant: £258,458 | Date of award: July 2016

Overview

Prof Chris JonesPaediatric glioblastoma (pGBM) and diffuse intrinsic pontine glioma (DIPG) are devastating brain tumours that are incurable using existing treatments.

No progress has been made in improving prognosis for decades and new treatments are desperately needed to improve the outlook for young patients with these tumours.

In this project, Professor Chris Jones is trying to understand how these tumours resist treatment and spread throughout the brain.

His work is focusing on proteins known as histones; these are ‘spools’ around which the DNA in our cells is wound.

In childhood gliomas such as pGBM and DIPG, we know that certain mutations in the DNA disrupt an important code within normal brain cells called the ‘histone code’ which regulates the switching on and off of genes. This is normally done through a type of histone called H3.

Professor Jones and colleagues have identified a completely new way in which childhood gliomas disrupt the histone code, involving a partner histone called H4. They have found that by affecting H4, the cells switch off their capacity to repair damage to their DNA and may help neighbouring cells to move throughout the brain, helping the disease to spread.

The H4 changes have so far only been found in two cases of childhood glioma, as they are only present in a small proportion of tumour cells. The team is looking for more cases like this to discover the true extent to which this process is found in these cancers.

They will make specific cell models in the laboratory to help them understand how changes in H4 and H3 affect each other. They will use these models to work out how H4 changes affect DNA repair and cell movement. They will also try to identify drugs that kill glioma cells with H4 changes, so that they may be tested in the clinic.

About the research team

The PI and his staff are internationally recognised as leading experts in the field of understanding paediatric high-grade glioma and DIPG biology.
External reviewer
Chris Jones is Professor of Brain Tumour Biology at the Institute of Cancer Research. He is one of the UK’s leading experts in childhood brain tumours and specifically in DIPG.

The Jones lab also forms part of the INSTINCT network with the UCL Great Ormond Street Institute of Child Health and Newcastle University, co-funded by Children with Cancer UK. This new project takes advantages of the infrastructure put in place through INSTINCT as well as the existing state-of-the-art facilities at The Institute of Cancer Research.

Professor Jones is head of a Europe-wide working group on high-grade glioma and DIPG and as such has a European leadership role in generating new treatment approaches for these diseases and is well-placed to drive rapid dissemination of results and clinical translation.

This is a highly ambitious research plan but is largely well supported by preliminary data and by the strong research network surrounding Professor Jones.
External reviewer

What difference will this project make?

Paediatric glioblastoma and DIPG are two of the most dreaded childhood cancers.

All children who develop these tumours die from their disease. There is therefore obviously a desperate need to develop new treatments.

By understanding this new way in which these cancers behave, there is the possibility of identifying new drugs that may be trialled in these children.

Read more: About childhood brain tumours | The INSTINCT network | Other brain tumour projects

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