Preventing resistance to targeted therapies

High-grade gliomas (HGGs) are the most common brain cancer in adults. Despite aggressive treatment with surgery, radiotherapy and chemotherapy, patients with HGGs have an extremely poor prognosis. A number of targeted therapies have also been tested but have failed to improve outcomes for these patients, highlighting the urgent need to better understand the biology of these tumours and why treatments fail.

Preventing cell plasticity

Some cells within the brain are described as being 'plastic' because they have the ability to change their identity in response to changes in their environment. While brain plasticity is important for the normal functioning of the brain, it could also be part of the reason treatments fail in patients with HGGs. Researchers have theorised that HGG cells undergo plastic changes in response to treatment that enables them to survive. Understanding how these plastic changes occur is important in order to prevent them from happening.

Ion channels are small holes in the cell membrane that control the flow of small substances in and out of the cell, and are believed to play a role in cell plasticity.

In this project, Professor Terrance Johns' research team will be analysing ion channels in a large number of tumour samples from patients with HGGs in order to identify which ion channels are involved in cell plasticity. The team will then test whether blocking those specific ion channels with drugs can prevent plastic changes within the tumour and improve the effectiveness of treatments.

Paving new avenues of treating high-grade gliomas

This research aims to identify new drug combinations that are more effective and may improve survival for patients with HGGs. And by using treatments that are already approved and used in clinical practice, this process will be dramatically sped up.

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