Medulloblastoma is one of the most common childhood brain tumours. Current treatments for these tumours are harsh and have a huge impact on the quality of life for children diagnosed. This is why we urgently need new therapies.
INSTINCT
The INSTINCT research project was funded in 2014, led by researchers at the University of Newcastle, the Institute of Cancer Research (ICR) and Great Ormond Street Hospital (GOSH). This project focussed on exploring new ways to treat some of the most aggressive childhood brain tumours including diffuse midline glioma and high-risk medulloblastoma.
This project aimed to bridge the gap between understanding tumour biology in the laboratory and translating this into new treatments.
INSTINCT focussed on finding more targeted treatments for children to improve survival, reduce the severe side effects of treatment and improve children’s quality of life.
A £5 million grant from us and other charities, including Children with Cancer, Cancer Research UK (CRUK), Great Ormond Street Hospital Charity, Blue Skye Thinking, and Little Hero, supported this research.
Medulloblastoma
There are four groups of medulloblastoma: WNT, SHH, Group 3 and Group 4. Group 3 medulloblastoma carries the poorest prognosis of all four groups, and clinicians have limited treatment options.
Recent research from INSTINCT set out to identify key genetic changes and find effective targeted treatment approaches to treating Group 3 medulloblastoma.
Group 3 medulloblastomas are particularly aggressive tumours. But some tumours in this group have a genetic change that makes them more aggressive and effectively incurable. This genetic change is linked to a gene called MYC.
The MYC gene is involved in cell growth, division and survival, so changes in this gene can cause uncontrolled cell growth which leads to tumour formation.
What did the research find?
Led by Professor Steve Clifford at the University of Newcastle, this research studied over 1600 medulloblastomas that had changes to the MYC gene. This is the largest number of this type of tumour ever studied. The study showed critical differences in clinical outcomes for children diagnosed with medulloblastoma. It also identified specific groups of children who may be incurable, highlighting the need for new treatment approaches.
With this knowledge, researchers were able to explore a kinder and more effective way of treating this disease. Using pre-clinical models, they tested drugs that target the effect of the MYC gene to help slow tumour growth.
What’s next?
Currently, there are limited options for targeted therapies in medulloblastoma. But this research suggests that understanding how the MYC gene impacts cell growth, and using this as a target for novel treatments may be a new option. We now know that changes to the MYC gene cause uncontrolled cell growth and tumour formation, and that using drugs to starve the cells of essential nutrients they need to grow may help to slow tumour growth.
Research will continue to understand the best ways to treat these aggressive tumours. This may pave the way for future clinical trials to treat this group of medulloblastoma.
Medulloblastomas with MYC gene amplifications are one of the biggest challenges in paediatric oncology. In our latest studies, we have identified an important group of these tumours which are essentially incurable using current therapies, and how to recognise them diagnostically. These studies provide the essential diagnostic characteristics that can immediately be used to identify this critical tumour group in the clinic, as well as an important targetable mechanism for the development of new therapies aimed at improving their outcomes.
This research was published in the journal Neuro-Oncology on 8 October 2024.
Find out more about the research
Professor Steve Clifford
Professor Steve Clifford is the Chair of Molecular Paediatric Oncology and Director of the Newcastle University Centre for Cancer. Alongside Professor Chris Jones and Professor Darren Hargrave, he was a lead researcher on the INSTINCT project which aimed to find news ways to treat aggressive childhood brain tumours.