Brain Tumour Research has funded its first research programme focused on high-grade astrocytoma, hunting for new ways to stop the progression of the disease.
Astrocytoma, IDH-mutant, is a type of glioma – a brain tumour that arises from astrocytes, which are supportive glial cells in the brain. It is most commonly diagnosed in young to middle-aged adults. Astrocytoma, IDH-mutant, tumours are grouped into grades, with high-grade tumours being more aggressive.
As part of the recently announced £2.8 million investment at the Brain Tumour Research Centre of Excellence at the University of Plymouth, the research team will build on expertise in low-grade tumours to help find more effective treatments for high-grade astrocytoma.
Improving the impact of existing treatments
A team led by Dr Claudia Barros is investigating how to enhance the effectiveness of chemotherapy in high-grade gliomas, including high-grade astrocytoma.
After previous success in the Centre trialling drugs that block TEAD proteins - key regulators of cell growth - in low-grade tumours, Dr Barros’s team is now investigating whether these inhibitors can improve the effectiveness of chemotherapy in IDH-mutant gliomas.
TEAD proteins play a key role in regulating cell growth and survival, and when this process goes wrong, it can drive tumour progression and resistance to treatment.
Dr Barros, in collaboration with Centre Director, Professor David Parkinson, will explore blocking these proteins with inhibitors, both alone and in combination with conventional chemotherapy (temozolomide), in high-grade glioma stem cells to see if they could improve patient outcomes. She is also investigating what the differences are between low-grade gliomas and high-grade gliomas, and whether these can provide clues for treatments.
Stopping tumours from hiding from the immune system
The Centre has also recently recruited two new co-leads, Dr Ming Li and Dr Mahmoud Labib, each bringing expertise on high-grade tumours. Both research co-leads are focused on understanding the role the immune system plays in tumour growth, and how this could be targeted.
Dr Ming Li’s group is exploring a family of proteins called GBPs, which usually help fight infections but also seem to support tumour growth and help gliomas hide from the immune system.
In laboratory experiments using mice, Dr Li’s team is working to understand how GBPs influence both the tumour and its surrounding environment. They have already shown that removing specific GBP proteins reduces tumour size, prolongs survival and increases the beneficial immune cells infiltrating the tumour. They are now testing whether targeting these proteins in combination with immunotherapies can improve outcomes for patients.
A researcher in the Plymouth lab
Dr Labib’s lab is looking at the genes that control IL6 – a signal that the body uses to turn off the immune system. Some tumours produce IL6 to evade detection. Dr Labib has developed an innovative technique that allows him to turn on and off hundreds of different genes in tumour cells and then identify which ones control the secretion of IL-6. By pinpointing and blocking these pathways, the team hopes to make high-grade gliomas more vulnerable to treatment. This approach is currently being tested in animal models, with the aim of fast-tracking the most promising drugs into clinical trials.
Our Director of Research, Policy and Innovation, Dr Karen Noble said: “High-grade gliomas remain one of the toughest challenges in cancer research, with survival often measured in months. These new projects at Plymouth bring fresh hope. By uncovering the secrets of how these tumours start, grow and evade treatment, and by developing smarter, more targeted treatments, this research aims to change the outlook for people diagnosed with these devastating types of brain tumours.”
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