Research on children's brain tumours awarded £1.6m
6 July 2023
Experts at UCL, Queen Mary University of London and Great Ormond Street Hospital are aiming to develop revolutionary treatments for children diagnosed with low-grade brain tumours, following major new funding.
The research team have been awarded £1.6 million by The Brain Tumour Charity to advance knowledge of low-grade brain tumours, how they behave in the body, how to better treat them and how to improve quality of life for children affected.
The research will be carried out in collaboration with researchers at the German Cancer Research Centre (DKFZ) and will continue the ground-breaking work of The Everest Centre*, following a second total investment of £5 million by The Brain Tumour Charity.
More than 400 children are diagnosed with a brain tumour each year in the UK. And, of these, approximately half are low-grade tumours.
Kinder and more effective treatments are needed as 20% of children do not survive for more than 20 years following a diagnosis. The current standard of care, which includes chemotherapy, radiotherapy and high-risk surgery, has a significant impact on a child’s quality of life.
Scientists at UCL will focus their research on tumour biology to understand the genetic make-up of low-grade tumours as this will help to improve the precision of diagnosis and work towards more personalised treatments to benefit patients.
They will also compare key features of low-grade paediatric brain tumours with other tumours in children and will explore how brain tumours protect themselves from the immune system and resist treatment.
Professor Tom Jacques (UCL Great Ormond Street Institute of Child Health) said: “Advancing our understanding of the molecular biology of these tumours will improve the ways in which we can clinically manage treatment. A deeper understanding of low-grade tumours will help us identify targets for new potential treatments.
“Our collaborations in the UK and Germany will allow us to harmonise diagnostic practises across Europe which will benefit those newly diagnosed. And the more data we collect about the genetic make-up of low-grade paediatric brain tumours will only further our ability to give children and their families more hope.
“This is a very exciting project and we look forward to working with everyone at the Everest Centre.”
Research will also focus on improving understanding of how tumour growth is controlled in the body and how ‘sleeping’ (also known as senescent) cells influence tumour growth and respond to treatment, which could help improve treatment options in the future.
Novel artificial intelligence (AI) systems will be developed to improve diagnosis of low-grade brain tumours. Using AI could be particularly useful in countries where molecular testing of tumours is costly.
The researchers at UCL will also play an important role in translating laboratory science into direct patient benefit. They will support the establishment of an innovative clinical trial, known as EPILOGUE, to identify new treatment options for patients.
Ulixertinib, a first-class drug recently discovered by scientists at The Everest Centre as a potential new treatment for low-grade brain tumours in children, will be one of the first drugs tested in the EPILOGUE trial.
Professor JP Martinez-Barbera (UCL Great Ormond Street Institute of Child Health) said: “Thanks to funding from The Brain Tumour Charity, our achievements so far lay down a strong foundation for developing new approaches to treatments for children with low-grade brain tumours.
“Our research aims to use knowledge already gained from work at the Everest Centre to further understand the role of senescence in low-grade brain tumours and identify new vulnerabilities of these brain tumour cells in order to explore novel treatment options for children.
“Our collaborations within UCL, and with partners at Queen Mary University of London and in Germany will enhance our research capability and truly improve options for children with a low-grade brain tumour diagnosis.”
A new quality of life questionnaire will also be introduced to help fully understand the effect of treatments on children.
Professor Darren Hargrave (UCL Great Ormond Street Institute of Child Health) said: “Children diagnosed with brain tumours do not have the outcomes that children with other types of cancer have, and better and kinder treatments are a priority.
“The standard treatment for low-grade brain tumours can include multiple rounds of treatment – including surgery, chemotherapy and radiotherapy – for many years of their lives, and that often has profound long-term effects on their health.
“We want our research to improve the lives of children diagnosed with a brain tumour, and the research we are going to carry out with this funding will enable us to do this.
“It is so important to translate the research we do in the labs into better outcomes for children.”
Meanwhile, researchers at Queen Mary University of London (QMUL) will investigate how tumour cell growth is controlled by the MAPK signalling pathway – a molecular cascade that controls the way cells multiply, survive and die, and is the most frequently altered pathway in paediatric low-grade brain tumours.
*The Everest Centre for Research into Paediatric Low-Grade Gliomas was established in the UK and Germany in 2017 with an initial £5 million funding from The Brain Tumour Charity. It brings together pioneering brain tumour scientists from DKFZ in Germany and UCL and QMUL in London.
Zachery Eckworth, now 11 and living in Basingstoke, Hampshire, was just 14 months old when he was diagnosed with an optic nerve glioma.
Zac was growing up just like any boy his age, until his parents, Miriam and Colin, noticed his eye was wobbling. Zac’s parents took him to see the GP who referred him straight to the eye clinic as Zac had banged his eye a few weeks before.
The clinic sent Zac to the local A&E where he had an MRI scan and after an overnight stay, Zac was diagnosed with an optic nerve glioma. These tumours are slow growing and grow in or around the optic nerve, which connects the eye to the brain.
Zac was referred to specialists at Great Ormond Street Hospital the week after his diagnosis where he had to have several rounds of chemotherapy. This was especially difficult because Zac was allergic to some of the chemotherapy drugs and in total had 5 different rounds of treatment.
After the first round of chemotherapy, Zac’s tumour remained stable for nine months, but then it kept growing, and more rounds of chemotherapy were necessary.
Miriam, Zac’s mum, said: “This was a very difficult time for the family. It was hard for Zac and it was hard for us to see him unable to be a child. Our daughter had just been born as well, and we knew the difficulties that chemotherapy would bring for Zac.”
There was some light at the end of the tunnel for Zac and his family. Zac’s tumour was biopsied and was found to have the BRAF-V600E mutation which activates the MAPK signalling pathway, leading to cells dividing uncontrollably and tumour growth. Knowing which mutation to target, Zac’s medical team put him on a trial treatment drug known as dabrafenib. Zac responded well to this drug and has been taking it since he was five.
Zac will remain on this treatment until his teenage years, when doctors will try to stop treatment and monitor how the tumour responds. There was a brief period where treatment was stopped, but the tumour began to grow again, so Zac was put back on it. Zac’s tumour responded well to dabrafenib, and shrank considerably.
Miriam said: “Every day we feel blessed to have been given this life-changing treatment option. It has given Zac the chance to live a relatively normal life. We are incredibly grateful to Professor Hargrave and all of his work and we are thankful for the research that means Zac can do so many of the things 11 year old boys do.”
Zac is substantially visually impaired as a result of his brain tumour. He suffered from hydrocephalus, a build-up of fluid on the brain, and also had lots of chemotherapy at a young age. His school is very supportive and day-to-day he learns braille and they provide him with large print. He also enjoys playing goal ball – a visually impaired sport.
Zac lives with the after-effects of his tumour but he doesn’t let it impact his life too much. He is nearly a black belt in karate. This helped him to build his confidence after surgery. He plays the keyboard and loves to be a DJ in his spare time. He also loves playing video games with his friends.
Miriam said: “Zac has a good quality of life, which allows him to recover emotionally from what he experienced in his younger years. He is able to live a relatively normal life which allows him to have his own identity – this treatment has given him that, it has given us more quality time as a family.
“We are so thankful for the research that has allowed this and praise the work of Professor Hargrave."
- Professor Darren hargrave's academic profile
- Professor JP Martinez-Barbera's academic profile
- Professor Tom Jacques's academic profile
- UCL Great Ormond Street Institute of Child Health
- UCL Population Health Sciences
- Credit: Liudmila Chernetska on iStock
E: p.danby [at] ucl.ac.uk