Researchers unlock new treatment options for babies with brain tumours

An international collaboration including researchers from the UCL Great Ormond Street Institute of Child Health (ICH) has found brain tumours in babies are biologically different to those in older children and could be targeted by existing medications.

This new understanding is set to change the World Health Organization’s diagnostic guidelines for infant brain tumours and could help some children avoid the need for intensive treatment such as chemotherapy.

Published today in Cancer Discovery, this research is one of the most comprehensive studies on infant brain tumours, involving samples from 241 patients from around the world. Although these tumour samples looked similar under the microscope, scientists revealed that 54 percent were distinct, having entirely different genetics. More than half of those distinct samples had specific genetic weaknesses – known as ALK and NTRK gene fusions – which could be targeted by existing medications.

This research provides a new understanding of an aggressive type of brain tumour, called a glioma. These types of tumours in infants are not only distinct from other tumours but act differently depending on the age of the affected child.

Babies which are in their first year of life seem to have a much greater chance of survival – with two thirds surviving more than 5 years - than those who are diagnosed later in life.

This study has uncovered that the genetic differences in tumours of younger children may explain why they are less aggressive. It could also help to identify affected babies who may not require chemotherapy, which can be harmful to the young developing brain.

“Although chemotherapy is a very good treatment option for some brain tumours in infants, there are side effects. With further research I’m hoping we can find more targeted, kinder treatment options for all children with brain tumours” said Professor Tom Jacques, Institute of Child Health.

This research involved samples from around the world from children who were diagnosed with glioma brain tumours and was led by The Institute of Cancer Research, London with support from colleagues at Hopp Children’s Cancer Center Heidelberg in Germany, the UCL Great Ormond Street Institute of Child Health, and St. Jude Children’s Research Hospital in the USA.

After identifying those tumours with ALK weaknesses, the team tested the effects of an ALK inhibiting drug on mice in the laboratory and found that it significantly reduced tumour size and outperformed chemotherapy.

Next, the team grew mini tumours in the lab from patients’ samples with NTRK gene fusions and found that they responded well to NTRK inhibiting drugs.

Two children whose brain tumours were found to have the NTRK gene fusion, were successfully treated with targeted medications, offering further evidence and promise for a more personalised targeted treatment approach in the future.

“This collaborative study has shown that we may not only be able to offer kinder treatments to infants, but also offer effective and more personalised treatments for children with other life-threatening tumours too”, said Professor Jacques.

More clinical trials are due to be set up to help to better understand tumor biology and further test NTRK and ALK targeted therapies.

This work was funded by charities including the CRIS Cancer Foundation, The Brain Tumour Charity, Children with Cancer UK, Great Ormond Street Hospital Children's Charity, and Cancer Research UK. Research using human cells and patients at GOSH and the ICH is underpinned by support from the National Institute of Health Research (NIHR) GOS Biomedical Research Centre (BRC).