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Preventing resistance to targeted therapies
Official title: Preventing resistance to targeted therapies using ion channel drugs
Lead researcher: Professor Terrance Johns
Where: Telethon Kids Institute Cancer Centre, Perth, Australia
When: June 2018 - May 2020
Cost: £116,285
Research type: Paediatric, High Grade, Academic
Some cells in the brain are described as being 'plastic' because they have the ability to change their identity in response to changes in their environment. High grade gliomas (HGGs) grow from glial cells, a type of cell in the brain that supports and protects nerve cells. Glial cells may play an important role in brain plasticity, which is how the brain adapts, learns and stores information.
While brain plasticity is important for the normal functioning of the brain, it could also be part of the reason why treatments fail in patients with HGGs. Researchers think 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.
Children affected by other types of cancers have experienced an increase in survival and improvement in their quality of life after receiving 'targeted treatments'. Targeted therapy is when a drug changes a specific aspect involved in the growth and spread of cancer.
In comparison, children with HGGs have an extremely poor prognosis despite aggressive treatment with surgery, radiotherapy and chemotherapy. A number of targeted therapies have been tested for these children, but they've failed to improve outcomes, highlighting the urgent need to better understand the biology of these tumours and why treatments fail.
Who will it help?
This research will help identify new drug combinations that are more effective and may improve survival for patients with HGGs.
This project started in June 2018 and the researchers are in the midst of analysing the tumour samples to identify the various classes of ion channels that contribute to treatment resistance. Once they've identified a list of ion channels, the team will determine if blocking these channels has anti-tumour activity.
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Treating brain tumours in children
Research into childhood brain tumours
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Researcher bio
Professor Johns was appointed the Head of the Telethon Kids Institute Cancer Centre in 2017. He has established the Brain Cancer Discovery Collaborative, an Australia-wide consortium of researchers and clinicians working to ensure that promising therapeutic discoveries are translated into the clinic for the treatment of patients with brain cancer.