The Institute of Cancer Research

The Brain Tumour Research Centre of Excellence at The Institute of Cancer Research, located in Sutton, south west London is working on the identification, assessment and validation of new therapeutics for paediatric-type diffuse high-grade gliomas (PDHGG). The team is led by Professor Chris Jones, a world-leading researcher in paediatric oncology, who is also the preclinical lead in the CONNECT consortium.

What is the Centre focused on?

The Centre will generate the laboratory data needed to support the application and launch of new clinical trials for children and young adults with paediatric-type diffuse high-grade gliomas (PDHGG). The preclinical data produced will act as a crucial bridge between basic biology research and clinical benefit for children and young adults with these tumours, which include those previously known as brainstem glioma and diffuse intrinsic pontine glioma, DIPG.

Here is Professor Chris Jones welcoming you to the Brain Tumour Research Centre of Excellence at The Institute of Cancer Research

How will it achieve its aim?

The team will assess the best therapeutic ideas from its own lab and others, as well as from drug companies, and select those most likely to be beneficial to patients
These new approaches will be tested thoroughly to produce as much high-quality pre-clinical data as possible in the shortest feasible time, including validation of targets, safety and efficacy/”does it work?”
They will assess their results using their jointly-developed, internationally-agreed guidelines
The Centre will then help prioritise the most promising approaches for clinical trial within established CONNECT platforms across the consortium worldwide

How will this Centre benefit patients and the brain tumour research community?

There are no effective treatments for paediatric-type diffuse high-grade gliomas (PDHGG) and the prognosis for children and young adults with this disease is very poor. For most of these tumours, the median survival is only nine to 18 months, with two-year survival rates of less than 5% of patients with certain subtypes. New therapeutic options are desperately needed.

To improve the outcomes of children and young adults with these devastating tumours, the Centre acts as an international hub for the development of new treatments, accelerating more therapies into clinical trials. The goal is to get treatments into trials within the next five years.

The new Centre also links with our network of Brain Tumour Research Centres of Excellence, and with other national and international groups through CONNECT, for which Professor Jones is the preclinical lead. This will build a collaborative network of paediatric brain tumour research groups, sharing and accelerating research.

Dr Karen Noble, Director of Research, Policy and Innovation at Brain Tumour Research, said:“This Centre will act as an international hub for the development of new treatments for children and young adults with these terrible brain tumours. Improving outcomes for those affected with these types of tumours is crucial if we are to make progress and bring much-needed hope to so many.”

Shayen's story

Niki O’Dea Patel from Bedfordshire lost her son Shayen to a high-grade brain tumour in September 2020, less than two years after his diagnosis. He was just 13.

“As a parent told your child has a brain tumour, you assume in this day and age there will be something to increase the odds and give you hope. The harsh reality is with this type of tumour there are no such treatments,” she said.

“I can’t believe that funding for research into brain tumours continues to be so poor. I am delighted that Brain Tumour Research is funding this important work but we will continue to press for the Government to act now and increase investment to help charities fighting to find a cure for this devastating disease.”

This vital research would not take place without the funding from Brain Tumour Research and our generous supporters.

If you would like to support our work to find a cure for all types of brain tumours, including PDHGG and other paediatric brain tumours, please donate.

Donate

What are paediatric-type diffuse high-grade gliomas?

Gliomas are the most common central nervous system (CNS) tumours in children and adolescents, and they show an extremely broad range of clinical behaviour, and can be high-grade (malignant) or low-grade (non-malignant). They form from what are known as precursor or progenitor cells, which during normal brain development go on to form either the neurons or the non-neuronal support cells of the CNS known as glial cells. Glial cells are made up of a variety of cell types, such as astrocytes, oligodendrocytes and ependymal cells, all of which have a large number of essential roles in maintenance and function of the CNS.

Historically, paediatric gliomas have been both grouped with adult gliomas, i.e. paediatric glioblastoma, and separate to adult gliomas, i.e. diffuse pontine intrinsic glioma. However, there is now a lot of literature confirming that paediatric gliomas have different molecular pathological features from adult glioblastomas, therefore in the new World Health Organization (WHO) 2021 CNS Tumour Classification paediatric gliomas are classified separately from adult gliomas and are divided into low-grade (1-2) and high-grade (3-4) groups.

Paediatric high-grade gliomas are now classified as “Paediatric-type diffuse high-grade gliomas” and include:

Diffuse midline glioma, H3 K27-altered
Diffuse hemispheric glioma, H3 G34-mutant
Diffuse paediatric-type high-grade glioma, H3-wildtype and IDH-wildtype
Infant-type hemispheric glioma

Each of these high-grade gliomas are distinct from one another and, as such, have different features and prognosis. More information can be found here.

Childhood brain tumours (high-grade) infographic

Copyright: Children’s Cancer and Leukaemia Group and Brain Tumour Research

What is CONNECT?

COllaborative Network for NEuro-oncology Clinical Trials conducts clinical trials in high-risk paediatric brain tumours (such as diffuse midline glioma) to investigate combinations of novel drugs with traditional therapies. It is a global partnership of world-class childhood cancer centres and paediatric neuro-oncology experts. Find out more about the Connect Consortium.

This vital research would not take place without the funding from Brain Tumour Research and our generous supporters.

If you would like to support our work to find a cure for all types of brain tumours, including PDHGG and other paediatric brain tumours, please donate.

Donate

References

Capper, D., Jones, D. T. W., Sill, M., Hovestadt, V., Schrimpf, D., Sturm, D., Koelsche, C., Sahm, F., Chavez, L., Reuss, D. E., Kratz, A., Wefers, A. K., Huang, K., Pajtler, K. W., Schweizer, L., Stichel, D., Olar, A., Engel, N. W., Lindenberg, K., Harter, P. N., … Pfister, S. M. (2018). DNA methylation-based classification of central nervous system tumours. Nature, 555(7697), 469–474. https://doi.org/10.1038/nature26000

P. S. J. D. Sturm. D, "Paediatric Gliomas: current concepts on diagnosis, biology, and clinical management," Journal of Clinical Oncology , vol. 35, no. 21, pp. 2370-2377, 2017.

Mackay, A., Burford, A., Carvalho, D., Izquierdo, E., Fazal-Salom, J., Taylor, K. R., Bjerke, L., Clarke, M., Vinci, M., Nandhabalan, M., Temelso, S., Popov, S., Molinari, V., Raman, P., Waanders, A. J., Han, H. J., Gupta, S., Marshall, L., Zacharoulis, S., Vaidya, S., … Jones, C. (2017). Integrated Molecular Meta-Analysis of 1,000 Pediatric High-Grade and Diffuse Intrinsic Pontine Glioma. Cancer cell, 32(4), 520–537.e5. https://doi.org/10.1016/j.ccell.2017.08.017

Clarke, M., Mackay, A., Ismer, B., Pickles, J. C., Tatevossian, R. G., Newman, S., Bale, T. A., Stoler, I., Izquierdo, E., Temelso, S., Carvalho, D. M., Molinari, V., Burford, A., Howell, L., Virasami, A., Fairchild, A. R., Avery, A., Chalker, J., Kristiansen, M., Haupfear, K., … Jones, C. (2020). Infant High-Grade Gliomas Comprise Multiple Subgroups Characterized by Novel Targetable Gene Fusions and Favorable Outcomes. Cancer discovery, 10(7), 942–963. https://doi.org/10.1158/2159-8290.CD-19-1030

Sturm, D., Pfister, S. M., & Jones, D. T. W. (2017). Pediatric Gliomas: Current Concepts on Diagnosis, Biology, and Clinical Management. Journal of clinical oncology: official journal of the American Society of Clinical Oncology, 35(21), 2370–2377. https://doi.org/10.1200/JCO.2017.73.0242