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The childhood brain is a complex and rapidly developing organ. Understanding how brain tumours interact with surrounding tissue provides insights into tumour growth.
Establishing tumour microenvironment models of paediatric brain tumours
Dr Elizabeth Coyle
University of Nottingham
Nottingham, NG7 2RH
15 January 2024
36 months
£349,209.83
Dr Beth Coyle and her team are investigating this interaction between tumour cells and their environment which will provide understanding into how a tumour develops and grows and will help in identifying cellular pathways that can be targeted by therapies without damaging healthy tissue. The location of tumours within the brain poses huge challenges for therapy. Current surgical therapies can be damaging to the developing brain and both radiotherapy and chemotherapy can also cause long-term intellectual and neurological damage. Dr Coyle’s team seek to provide a better way of studying brain tumours so that we can develop better ways of treating them without this long-term impact on brain development.
Currently, scientists analyse brain tumour cells in isolation, and this does not give an accurate picture of how the tumour would grow in the patient’s brain. Neither does it give a good representation of how that tumour will respond to therapies. This research project has three main aims. Firstly, the team wish to create accurate and personalised laboratory models of the environment surrounding a patient’s brain tumour. Secondly, the team will use these models to examine how the local brain environment supports tumour growth. Thirdly, the team will utilise this knowledge to target the tumour growth without damage to the surrounding tissue. Combining these three aims will not just provide a clearer understanding of what drives a tumour to grow and spread in a patient’s brain, it will also help us identify the therapies that maximise damage to the tumour whilst minimising damage to its surroundings.
Children with brain tumours and their families face the spectres of cancer diagnosis and therapy that is often sadly ineffective. Even where we can successfully treat childhood brain tumours there is often a significant long-term effect of the therapy with neurological and developmental impacts. This project hopes to bring benefits to young people with cancer: firstly to bring about a better understanding of brain tumour development and what cellular pathways drive this, and secondly to use this information to identify treatments that spare healthy tissue whilst hitting those pathways that support the growth of the tumour.
Knowledge gained from this project can then be used to identify chemical inhibitors of these processes that can in turn be tested in our models. This will help to significantly accelerate identification and testing of new treatment approaches.
Brain tumour biology is hugely complex and understanding this requires a team of researchers with expertise in different areas. Dr Beth Coyle and her research team bring together expertise to work towards the shared goal of improving outcomes for children and young people with brain tumours.
Beth has been at the forefront of children’s brain tumour research in the UK for more than 20 years. She is a long-term member of the Nottingham Children’s Brain Tumour Research Centre which allows clinical and scientific researchers to pool their expertise towards better understand and treatment.
The research will take place in the University of Nottingham’s Biodiscovery Institute, a state of the art multidisciplinary research facility where the majority of the applicants are co-located.
Joining Dr Coyle’s team for this project are experts in generating the matrices needed to study 3D tumour growth accurately (Professor Alvaro Mata, School of Pharmacy), in studying the interaction of tumours with the immune system (Dr Andrew Jackson and Dr Judith Ramage, both School of Medicine), hypoxia (Dr Alan McIntyre, School of Medicine) and in understanding how drugs target cellular pathways in tumours (Dr Ian Kerr, School of Life Sciences and Dr Louise Fets, MRC London Institute of Medical Sciences).
The team is completed by a paediatric oncology clinician (Dr Tim Ritzmann, University of Nottingham/ Nottingham University Hospitals NHS Trust) and a neuropathologist (Mr Simon Paine, Nottingham University Hospitals NHS Trust) whose expertise at the interface between the clinical bedside and the laboratory bench will contribute greatly to ensuring the models we make are excellent mimics of the patient’s brain tumour.
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