Study explores enzymes’ role in brain tumour growth and therapies

Researchers will complete a pre-clinical evaluation of three drugs already being used to target aldehyde dehydrogenase enzymes in other conditions
Libby Hasell-Williams, PhD research in the Brain Tumour Research Centre of Excellence at the Â鶹´«Ã½, has received funding through the Young Investigator Award programme run by the the Children’s Tumor Foundation (CTF)
Aldehyde dehydrogenases (ALDH) are a group of enzymes shown to be connected to cancer cell growth. Until this point, however, there has been no research into their role in the development of some types of brain tumours and whether specific therapies could be developed that will benefit people with these forms of cancers.
A new study aims to address that by identifying the role ALDH enzymes play in brain tumours – and beginning to explore the most effective ways to target them. The research is being led by PhD researcher Libby Hasell-Williams and Professor of Neuroscience Professor David Parkinson , both working in the Â鶹´«Ã½â€™s Brain Tumour Research Centre of Excellence.
A two-year study, it will be supported by the . The research will be split into two phases, starting by carrying out a detailed investigation of the role of ALDH1A3 – a type of ALDH enzyme that plays a crucial role in development, metabolism and other biological processes – in the growth of meningioma and schwannoma tumours, two important types of tumour in the human nervous system.
It will then complete a pre-clinical evaluation of three drug compounds that have already been shown to inhibit ALDH in relation to other medical conditions and been identified – through in vitro studies carried out by the research team and elsewhere – as having the potential to be effective in targeting the proliferation and survival of meningioma tumour cells.
Unlike any previous studies, this new work will involve tests into the effectiveness of the drugs on human tumour cell models – taken from the Â鶹´«Ã½ Tumour Biobank – and could ultimately result in the expanding and upscaling of drug trials in the future.

Aldehyde dehydrogenases are a group of enzymes that are normally really helpful in our bodies but in cancers, they become overactive.

While there is a lot of work exploring the impact that has in relation to other cancers, no-one has really looked at them in relation to meningioma and schwannoma. Through the work we have done so far, we have confirmed these enzymes contribute to the growth and survival of cells, and will now be looking at the use of inhibitors to reduce this growth. We have really exciting preliminary data and it is wonderful to get this funding so we can continue our studies.
PhD researcher Libby Hasell-Williams 2.jpg

Libby Hasell-Williams
PhD researcher, Brain Tumour Research Centre of Excellence

The new study builds on existing work at The Brain Tumour Research Centre of Excellence at the Â鶹´«Ã½, which has seen it become internationally renowned for research into low-grade tumours that are usually slow-growing and frequently affect children and young adults.
Much of its work centres around meningioma, which affect 2,790 people in England each year. And while most are low-grade and non-cancerous, they can still cause serious and sometimes life-limiting complications due to their location and size within the nervous system.
Brain tumours kill more children and adults under the age of 40 than any other cancer. There are more than 100 different types of brain tumour, making them notoriously difficult to find effective treatments for.  

This line of research is one of a number of projects through which we are trying to identify different therapies that could be used to treat meningioma and schwannoma tumours.

Thanks to Libby’s work to this point, we have found what we believe might be an Achilles heel for the tumour cell that could enable us to develop treatments, which are tumour specific. These tumours are slow growing and patients potentially have to live with them for months or years. We need something with low toxicity, and in future the work we are doing through this project could form part of some form of a single or combination therapy.

David ParkinsonProfessor David Parkinson
Professor of Neuroscience

 

Beginning a career in brain tumour research

I became really interested in cancer research during my A-levels, and there are big developments happening every year that are changing people’s lives. It is such a fast-evolving field, and one that is really exciting to be part of from a scientific perspective.
I thought the BSc (Hons) Biomedical Science course would be the ideal one to help me start my career. During that, we studied the fundamentals of cell biology and broader anatomy, and I then started to focus more on my personal interest in cancer research during my third year.
After graduating, I decided I wanted to do a PhD, under the supervision of Professor David Parkinson , funded by the charity Brain Tumour Research at their Â鶹´«Ã½ Centre of Excellence. I will be looking at the role of aldehyde dehydrogenase (ALDH) enzymes in brain tumours.
It is quite a new area, so a lot of the work is exploratory, and my work so far has involved a mixture of literature reviews and research in the labs. That has enabled us to confirm ALDHs are present and metabolically active in brain tumours and contribute to the growth and survival of tumour cells.
What we are really trying to do now is prove that compounds inhibiting these enzymes can be safe and effective possible therapies, that could ultimately benefit meningioma and schwannoma patients.

I have recently completed my PhD research, and it is really lovely to get the funding from the Children’s Tumor Foundation to continue my work. Meningioma and schwannoma are under researched, and it is a field that I have become really connected to – I already feel I have accomplished quite a lot, but want to see it taken further.

Libby Hasell-Williams
 
The grant was awarded through CTF’s , a cornerstone grant program at the Children’s Tumor Foundation that supports early-career scientists and clinicians pursuing bold ideas with the potential to drive progress across all forms of NF. This project is one of several funded through this year’s YIA program, which is advancing research in gene therapy, tumour biology, learning challenges, and cancer neuroscience.
“The Young Investigator Award is designed to spark new thinking in NF research and help launch early-career scientists into independent research careers. By supporting researchers like Libby, we’re investing in the future of NF2 science and advancing the search for more targeted, effective treatments.â€
 
Vidya Browder, PhD
Director of Research at the Children’s Tumor Foundation
“NF2-related tumors, especially those in the brain, are difficult to treat and can severely affect quality of life. By investing in early-stage research like this, we’re opening doors to new scientific breakthroughs – and ultimately, better treatments for patients.â€
 
Annette Bakker, PhD
Chief Executive Officer of the Children’s Tumor Foundation
Brain Tumour Research provides long-term funding to dedicated key academic institutions. This stable funding enables researchers to deliver on their innovative research which will lead to transformational impact, better treatments and improving outcomes for people affected by brain tumours.  
“Libby’s work is a perfect example of the vital research which will one day lead to better treatments for patients with these devastating tumours. But without greater and sustained investment in brain tumour research, talented scientists like Libby will face uncertainty about the future of their work. Working together is vital if we are to make the change so desperately needed to improve survival rates, accelerate research, and ultimately find a cure.â€
 
Dan Knowles
CEO of Brain Tumour Research
 

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