No brain tumour ignored

Fast facts

Official title: Curing the underserved – developing transformative therapies for rare childhood brain tumours
Lead researcher: Prof Richard Gilbertson
Where: University of Cambridge, UK
When: April 2019 – April 2025
Cost: £1.5 million over 5 years
Research type: Paediatric, Academic, Translational, Ependymoma and Choroid Plexus Carcinoma (High grade)
Grant round: Quest for Cures

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Choroid plexus carcinoma (CPC) and supratentorial C11orf95-RELA ependymoma (ST-EP-RELA) are aggressive paediatric brain tumours that can have a poor prognosis. No new treatments have been developed in the last 30 years, and even ‘standard’ therapy remains largely ineffective. New therapies have not yet been discovered due to the rarity of these two tumour types

What is it?

As current standard of care has not worked for these tumour types, this project will focus on testing new models and finding new treatments for both CPC and ST-EP-RELA. Professor Gilbertson and his team have previously tested over 1.2 million molecules against brain tumours to find promising molecules that can be used to create new drug treatments for CPC and ST-EP-RELA. They will continue doing so to find new drug treatments for these rare tumours.

Additionally, these researchers have already found that two drugs – which have entered the late stage of development where clinical trial testing is the next step before entering the market – have shown great promise to treat these tumours. The team will now develop a plan to bring these drugs to the clinic, with the goal of setting up clinical trials. To ensure that these drugs effectively target the tumour, the researchers will experiment with mixing these drugs with gels that will fill the space left by the tumour after surgery. They will also see if they can make use of tiny tubes in the brain, called catheters, that can be repurposed to transport the drugs throughout the brain. They will carry out these experiments and testing on preclinical models for CPC and ST-EP-RELA that have been newly developed in-house by the team.

Why is it important?

This grant will allow Professor Gilbertson’s team to concentrate their efforts on making new discoveries to help children with these tumours. The way the lab’s set up and the collaborations already in place will mean that any new discoveries are brought to the clinic as quickly as possible.

Who will it help?

Currently children with CPC and ST-EP-RELA are given the same treatment as children with other types of brain tumour. This is because there are no precision treatments for these rare tumours.

This research programme will give children affected by these diagnoses, and their families, hope for more effective treatments and, ultimately, increased survival.

Milestones

Year 1

• Made two preclinical models of ST-EP-RELA tumour cells which they are currently testing to study how tumours development.
• The researchers are beginning to design new drugs for ST-EP-RELA and they will ensure they are specifically effective against ST-EP-RELA tumours.
• For CPC they have found a promising new drug which will be effective against it when treated alongside radiotherapy and surgery treatments.

Year 2

• The team successfully developed preclinical models for ST-EP-RELA that develop tumours spontaneously. This allows the models to be more accurate to patients.
• Continued working on new drugs for CPCs and they have seen promising results when paired with radiotherapy and surgery.
• Identified small molecules in ST-EP-RELA cells which appear to be promising targets for new targeted drugs.
• The new alternative treatment method they have found consists of delivering drugs directly to the brain. They have strong evidence to suggest that using this method will be more effective and cause fewer side effects.

Year 3

• The research team used their CPC and ST-EP-RELA models to compare how these tumours develop differently to a normal brain in order find any new drug targets.
• They created other versions of their ST-EP-RELA model that they are using for different types of studies, such as replicating clinical trials with chemotherapies, radiation, and surgery.
• Identified drugs which work well against ST-EP-RELA and are working to modify them, to understand how they function in cells, before bringing them to pre-clinical studies. A specific drug worked especially well, they are now identifying if it can cross the blood brain barrier and reach the tumour.

Year 4

• The research team continue to work on their preclinical models for CPC, making sure they are as genetically similar to real CPC tumours as possible.
• They have been able to develop preclinical models of ST-EP-RELA which have the same genetic defect as patients.
• Developed a new computational method to understand how genes interact with each other to identify potential drug targets.

Year 5

• The research team have new models for ST-EP-RELA which are easier to work with than their previous models.
• Developed a way to identify effective combinations of chemotherapy and radiotherapy against CPC and ST-EP-RELA using computer models.
• The researchers are finding effective combinations of radiotherapy and chemotherapy for ST-EP-RELA and recurrent tumours.
• The team have tested drugs that are already available on the market and have found that they are capable of entering the brain. They will now investigate if they are effective at reducing tumour size.

If you have any questions about this, or any of our other research projects, please contact us on research@thebraintumourcharity.org