Elucidating brain tumour cell plasticity and preclinical treatment options during malignant progression and tumour recurrence

Rationale

Brain cancer is devastating for patients and their loved ones. Even with the best treatment, patients with the most cancerous brain tumours live for only 12 to 15 months, a much worse outcome than most other cancer types.

Treatment fails because brain cancer cells are very adaptive and grow finger-like projections into the surrounding healthy brain. Unlike in other cancers (e.g. breast), the brain cannot be cut out whole, so cancer cells always remain after surgery. These remaining cells resist being killed by radiation and chemotherapy, so new tumours eventually regrow.

Better anti-brain tumour treatment options are urgently needed, and our goal is to ultimately translate our most promising research findings into clinical applications. 

Plan of work and impact of our studies

In this project, three major research strands are being pursued that aim to better understand why cancer cells in the brain behave differently and what the most important (molecular) traits are that make some brain tumour cells more aggressive than others.

The aim is to gain insight into why and how brain cancer cells survive and grow despite therapy, and how to target the tumour cells more efficiently so that their growth can be halted. It is important to note that all the underlying cancer biology posing these questions is very dynamic and happening in a location and time-specific manner in the brain. 

Replacement

Despite the very best attempts of many researchers globally, it is challenging to recreate the journey that brain tumour patients go through in the research laboratory. Although it is preferable to avoid the use of animals, it is currently the only option to study brain tumour cells in their anatomical environment (niches in the brain), and to model the effects of surgery. Here, brain tumour implantation and tumour resection (surgery) models will be used in mice to mimic the patient journey from brain tumour development to neurosurgery and relapse. 

Reduction

Brain cancer cells taken (and grown) from patient tumours will be implanted into mouse brains. This system will allow us to study human cells in mice that have had their immune system weakened so that the cells can form a tumour, which can be complemented by mouse tumours in mice with a fully functional immune system. 

Refinement

The mice will have scans and undergo brain surgery whilst asleep. They will be monitored daily and humanely killed if showing signs of pain and distress. 

This project will increase understanding of the cells driving tumour growth and tumour recurrence, identify new treatment targets, and ensure that findings from the animal models are relevant to patients.

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