The INSTINCT programme is an innovative collaborative initiative between the Newcastle University Centre for Cancer, the UCL Institute of Child Health and the Institute of Cancer Research. INSTINCT aims to take forward vital research into the causes of high-risk paediatric brain tumours and find the best ways to treat them. Almost £1 million in funding from Children with Cancer UK has already led to major advances in understanding the biological characteristics of brain tumours.
What have been some of the major findings of the INSTINCT programme to date?
One of the key findings has been in relapsed medulloblastoma – the most common high grade childhood brain tumour. We have found common genetic changes that arise at relapse which can be used to predict tumour growth after relapse, so treatment can be more tailored in the future.
For high-grade glioma, we have discovered a drug combination to target two gene mutations in this disease, which we believe may only occur in children. We’ve recently completed a study of 1000 childhood gliomas to understand their genetic basis and identify key subgroups of tumours on which we can focus the development of new therapies.
Using tumour biopsies, we have examined the biological characteristics of primary atypical teratoid rhabdoid tumours (ATRT). Rhabdoid cells have also been grown in the lab and studied for weaknesses to new medicines. We’ve managed to achieve this by using viruses to artificially modulate a key mutation in rhabdoid cells and see how it causes tumours to grow. By finding these weaknesses, we can now test more targeted drugs and aim to bring these into clinical practice, if they are safe and effective.
We’ve also assembles a large group of rare tumour biopsies, sourced from hospitals across the UK, and have started analysing tumour samples at the cellular level to find any similarities between them. We have studied a large number of infant gliomas, many of which appear to represent a completely different type of tumour compared to older children.
What are some of the key impacts this research may have on treatment of paediatric brain tumours?
Our findings in medulloblastoma support the use of biopsy at relapse in routine clinical practice to direct palliative care and find more effective treatments. These genetic tests have been used by doctors at Great Ormond Street Hospital and it is exciting to see that this research is already making a difference to children with brain tumours.
In addition, our findings in ATRT will help shape new therapies to be tested pre-clinically and then in clinical trials with children with rhabdoid tumours. New clinical trials for high grade glioma patients will take into account the biological variations of the disease.
What is the overall significance of this research?
‘High-risk’ paediatric brain tumours are the leading cause of childhood cancer death. Biological discoveries, and their translation into more tailored therapies, will be essential to future clinical advances. The primary aim of this research is to find more effective treatment for high-risk childhood brain tumours. Ultimately this will lead to better treatments for patients.
This total value of the project is £4 million and is co-funded by Children with Cancer UK, The Brain Tumour Charity and Great Ormond Street Hospital Children’s Charity.