Background

Gliomas are a group of brain tumours that grow within the brain. Currently, most gliomas are treated with brain surgery to remove as much of the tumour as possible followed by chemotherapy and radiotherapy to treat the tumour that the neurosurgeon can’t remove. For the common gliomas, which are aggressive cancers, treatment prolongs life by months. 

 

New therapies are badly needed. 

 

Developing new treatments requires a much deeper understanding of the biology of brain tumours and how they interact with the surrounding brain. Laboratory models of brain tumours, such as those based on cell lines or transplants of brain tumours into mice, have failed to generate new therapies for brain tumours. 

 

We have developed an alternative strategy in which experiments are performed on a live sample of a person’s tumour outside their body. This enables us to undertake mechanistic studies of how human brain tumours behave in human brain tissue. Our approach has been adopted by recent recommendations for neuro-oncology research (Karschnia et al Lancet Oncol 2023)

 

Many of the clinical symptoms caused by gliomas, such as seizures or weakness, are due to damage to the surrounding brain. Therefore, curing brain tumours means treating the brain tumour and, also, the symptoms arising from the damaged brain.  

 

Results

We collect blocks of brain tissue or tumour fragments that are being removed as part of neurosurgery to excise the patient’s glioma (Kirby et al Neuro-oncol Adv 2020; Kirby et al Neuro-oncol Adv 2021). This is done with informed consent of patients and approval from the Human Research Authority. The tissue blocks extend from the surface of the brain into the glioma. The blocks of living human brain tissue are cut into thin slices (0.3 mm thick) and the glioma cells are labelled with a customized fluorescent marker. The marker enables us to see live glioma cells in live brain tissue slices under the microscope and, also, when the brain slices have been preserved and stained with markers for other types of brain cell. A major advantage of our live human glioma-brain slices is that we can study the glioma, the brain surrounding the glioma and how the glioma and brain interact.

 

Malignant progression of gliomas

Some gliomas, termed lower-grade gliomas, are indolent for several years before they become aggressive cancers. This process is referred to as malignant progression. We have used the glioma-brain slice to investigate the mechanisms underlying malignant progression. We found sparsely-distributed glioma hotspots in live glioma-brain slices, where the glioma cells have the features of aggressive tumour cells (Figure 1). We have proposed that the hotspots are the seedbeds of malignant progression (Kirby et al Neuro-oncol Adv 2021).

 

Epileptic discharges in the brain surrounding the tumour

Seizures are a common way that brain tumours come to clinical attention. We have recorded the spontaneous neural activity in the brain surrounding the tumour and have identified three different types of electrical discharge in the brain tissue. The longest lasting discharges (seconds) resemble seizures. We are currently studying what causes the epileptic discharges.

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