Instinct-MB

What is it?

New research targeting high-grade childhood brain tumours.

The INSTINCT-MB research project, led by Newcastle University, will aim to develop better and more effective treatments for medulloblastoma, a disease which results in approximately 30% of childhood sufferers dying. High-risk paediatric brain tumours are the leading cause of childhood cancer death. Whilst many advances have been made in treating the most common childhood brain tumours, current treatments still fail in a proportion of cases. Sadly, many children who do survive brain tumours are often left with severe, life-limiting disabilities as a result of the tumour and the aggressive treatments that are needed to save their lives.

Blue Skye Thinking, alongside charity co-funders Children with Cancer UK and Little Hero have announced their funding for a new landmark research programme with the aim of combating medulloblastoma (MB), the most common high-grade brain tumour in children.

Led by Professor Steve Clifford from Newcastle University Centre for Cancer, the research project will aim to identify and develop effective treatments against Group 3 medulloblastoma, combining different drugs alongside CAR-T cell therapies. The research project will be supported by the INSTINCT research network with UCL Institute of Child Health and The Institute of Cancer Research.

“One third of medulloblastoma patients are still incurable, and those that survive can suffer dramatic side effects due to current therapies, such as neurological disorders. This is still a big area that needs to be studied and a lot of improvement needs to be made.”

Dr Laure Bihannic, St Jude Children's Research Hospital

Why is it important?

One of the major specific challenges in childhood cancer is Group 3 medulloblastomas driven by the presence of a gene called MYC. This tumour group occurs almost exclusively in young children and is essentially incurable, contributing significantly to overall childhood cancer death rates. Advances in standard treatments such as chemotherapy and radiotherapy have helped to improve levels of survival overall but are not specific to tumour sub-types, and are ineffective against MYC-Group3 tumours. New therapies are therefore urgently needed to improve the outlook for children with high-risk medulloblastoma. The INSTINCT-MB project will seek to develop new treatments for Group 3 medulloblastoma, using new drugs and promising new immunotherapies known as CAR-T cell therapies.

Who will it help?

With the recent development of these new, targeted, therapies, there is a substantial opportunity to eliminate Group 3 medulloblastoma tumours. This type of tumour often has upregulated copies of the MYC gene which triggers rapid disease growth and often results in treatment failure. Tragically, fewer than 5% of children survive this disease. INSTINCT-MB researchers have identified potential drugs to target the MYC gene and have also pioneered promising CAR-T cell therapies to help the immune system destroy cancer cells. CAR-T cell therapy reprograms a child’s immune cells to identify and attack cancer, without damaging healthy cells. 

Crucially, the goal with new treatments for Group 3 medulloblastoma is to increase survival and cause less damage to surrounding healthy cells, greatly reducing long-term side-effects. Children and young people facing this devastating disease in years to come will be given hope of a healthy future.

“We urgently need all-new treatment approaches for childhood cancer types with the poorest prognosis.  By bringing together the essential network of world-leading experts necessary to develop such approaches targeted specifically against tumour biology and bring them to the clinic, we aim to bring about a step-change in the treatment and outlook for these patients”

Professor Steve Clifford, Northern Institute for Cancer Research, Newcastle

Milestones

Achieved

Principal Investigator Professor Steve Clifford provided an overview of some of the key discoveries from the INSTINCT programme to date

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.

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.

Upcoming