Trialling new therapies for brain tumours

Testing the effectiveness of new compounds and therapies and their effects on tumour growth and cell survival
Glioma stem cells with purple colouration

Trialling new therapies for brain tumours

Testing the effectiveness of new compounds and therapies and their effects on tumour growth and cell survival
Title: Trialling new therapies for brain tumours
Funded by: , , , Â鶹´«Ã½ R&D Solutions Fund 
Dates: Ongoing
Â鶹´«Ã½ PI: Professor David Parkinson  
 
This project involves using both our in vitro and in vivo models of different tumour types, such as schwannoma, meningioma, glioma and glioblastoma, to see how we can trial new therapies, new combinations of therapies and re-purpose known drugs to target tumour cell growth and survival. 
Through our expertise, we work with many pharmaceutical companies, both in the UK and abroad, to test new compounds for their efficacy in our tumour models. In this work, we begin by testing both in cell lines and in the primary tumour cells from human patients from our own Biobank, using 2D and 3D spheroid cultures. 
If compounds show promise here, then we translate this into our transgenic pre-clinical models for further testing and quantification to see if these can progress through to clinical trials. In such a way, we have successfully taken new compounds (e.g. TEAD inhibitors) from our experiments in vitro through to clinical trials.

A major part of our work is to translate the basic science in the lab into new treatments for patients. We can take our findings and design new treatments, both from our own work and in collaboration with pharmaceutical companies. Some of these drugs are newly discovered, whereas others may be repurposed drugs that allow an accelerated progression to trials with patients.

David ParkinsonProfessor David Parkinson
Professor of Neuroscience and Director of BTRC

Research questions

Could drugs make radiotherapy more effective for meningioma? 

Dr Juri Na is leading research into the mechanisms of radioresistance in meningioma cells, which reduces tumour responsiveness to treatment over time. Juri investigates the use of HDAC inhibitors and other radiosensitisers (such as FOXM1 inhibitors) in combination with radiotherapy to modulate the tumour microenvironment and improve outcomes in aggressive meningioma. 
Additionally, Dr Na is leveraging high-throughput screening of a comprehensive library of clinically approved cancer drugs to identify compounds that can synergistically enhance the efficacy of radiotherapy, with the aim of accelerating translational applications and uncovering novel combination strategies for meningioma treatment.

Can new drugs, combined with chemotherapy, improve treatment for glioma, meningioma and schwannoma tumours? 

Dr Claudia Barros and her team are investigating whether TEAD inhibitors, used alone or alongside chemotherapy, can make treatments more effective against glioma, including IDH-mutant types.
Professor David Parkinson and Dr Liyam Laraba, following on from their successful work with TEAD inhibitors, are trialling new drug combinations in meningioma and schwannoma tumours. They also collaborate with many pharmaceutical companies to test new drugs in these tumour types. 

Could MERTK inhibitors offer a non-invasive way to treat meningioma?

Dr Sylwia Ammoun investigated a group of proteins expressed at the cell surface called TAM family receptors – which consist of TYRO3, AXL, and MERTK receptors – in schwannoma and meningioma tumours. 
They found that MERTK and AXL are responsible for tumour cell proliferation and survival. In addition, they revealed that inhibiting MERTK decreases tumour cells' growth and survival and strongly reduces numbers of tumour-supporting immune cells. Dr Ammoun is currently testing repurposed medicines which target MERTK – a protein on the surface of tumour cells – in meningioma and schwannoma, aiming to move to clinical trials in the coming years. Several MERTK inhibitors are already in trials for other cancer types, offering hope that new treatments could be available soon.
MRX-2843, a promising MERTK inhibitor, is currently being tested by Dr Ammoun in 3D cultures of patient-derived tumour cells with Dr Emanuela Ercolano, and in mouse models in collaboration with Professor David Parkinson and Dr Liyam Laraba.

Could ancient viral DNA fragments embedded in the human genome contribute to schwannoma and meningioma growth and survival? If so, can currently available drugs inhibit this process?

Dr Sylwia Ammoun and collaborators have shown that ancient viral DNA fragments can become activated in schwannoma and meningioma tumours, promoting tumour growth and survival. Their work also demonstrates that anti-HIV drugs, long used in the treatment of HIV, can strongly counteract tumour growth and survival, and can enhance the effectiveness of other therapies. Notably, these effects were observed at concentrations roughly 10 times lower than those used for HIV treatment, suggesting that the drugs may be effective at much lower, non-toxic doses for patients.  
Two anti-HIV drugs, used in combination, are now being tested in clinical trials for patients with NF2-related schwannomatosis who have schwannomas and meningiomas. The trial is supported by the Children's Tumour Foundation, with Dr Sylwia Ammoun serving as a co-applicant alongside Professor Gareth Evans and the primary applicant, Professor Oliver Hanemann. The study is currently underway at Derriford Hospital in collaboration with Manchester Hospital. Dr Sarah Kingdon will assume responsibility for overseeing the trial from March 2026. 

Can repurposed drugs target ALDH proteins in meningioma and schwannoma? 

Professor David Parkinson and his team are studying whether drugs already approved for other conditions can block the activity of ALDH enzymes. These enzymes may play a role in the growth of NF2-related meningioma and schwannoma tumours. If successful, this approach could offer a new treatment option without the need to develop entirely new drugs.
 
 
 

Brain Tumour Research Centre

The internationally renowned Brain Tumour Research Centre (BTRC) focuses on low-grade tumours and investigates new mechanisms underlying brain tumourigenesis, including tumour initiation. 
We work truly from bedside to bench and back. We have a large biobank of stratified tumour samples and are using a variety of complementary tumour models. The BTRC encompasses research groups working closely together and complementing each other with both shared approaches and shared in vitro and in vivo models.
 
Glioma stem cells with bright colouration