New treatment hope for aggressive brain tumour

A drink given to patients prior to surgery, which differentiates between healthy brain cells and cancerous cells using florescent light, could be a major step in helping to treat a highly aggressive brain tumour.

The study, which is published today in the Neuro-Oncology Advances, is led by experts from the University of Nottingham’s Biodiscovery Institute.

Glioblastoma (GBM) is a highly aggressive brain tumour with an average survival time of only 14 months from diagnosis, despite a combined treatment of surgery, chemotherapy and radiotherapy. Identifying a new drug to treat GBM is severely hindered by ‘intra-tumour heterogeneity’, a term used to describe differences in biological information within distinct regions of a patient’s tumour.

Historically, drug targets for GBM have targeted the central, core tumour region which is surgically removed, on the assumption that the biology of this area reflects any remaining tumour left behind.

Current evidence suggests that these residual GBM cells which have infiltrated into the normal brain, likely have different genes switched on or off compared to the GBM core.

Attempts to identify genes within infiltrative GBM cells have been complicated by an inability to differentiate between genes from diseased cells and healthy brain cells.

In this new study, funded by the Brain Tumour Charity and led by Dr. Stuart Smith (Clinical Associate Professor of Neurosurgery) and Dr. Ruman Rahman (Associate Professor of Molecular Neuro-Oncology) at the University of Nottingham, experts have successfully isolated the GBM cells from normal brain cells and identified gene patterns unique to this tumour region, which are likely to be associated with re-growth of GBM.

Patients are given a drink prior to surgery, called 5-aminolevulinic acid (5ALA), to enable fluorescence guided neurosurgery. The liquid generates individually fluorescent tumor cells within a background population of non-fluorescing healthy brain cells.

Surgically removed tumour from GBM infiltrative regions is then separated from normal brain cells based on the fluorescence. The entire set of genes in the human genome from tumour and normal brain are then analysed.

Dr Ruman Rahman, one of the authors of the study, says: “Through our work, we have been able to identify the serpine1 gene as being switched on uniquely in the GBM infiltrative cells”. Exposing GBM cells to a drug which inhibits the protein encoded by serpine1, resulted in the GBM cells being less able to infiltrate the brain.

Our study offers hope to patients that isolation using 5ALA, may become a basis for identifying more effective drugs to target GBM cells, which more closely reflects the disease which remains in the brains of patients after surgery.”

A full copy of the study can be found here.

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