Targeted drugs could be used to treat some infants with high-grade glioma, according to the biggest study to date on the aggressive brain tumour.
The hope that babies could be treated without the need for chemotherapy is revealed today (2 April 2020) after scientists discovered that the tumours in babies are molecularly different from those in older children.
They say this could explain the difference in survival rate: babies who are diagnosed when they are less than 12 months old tend to have a better outcome, with about two thirds surviving five years or more. However, the fatality rate for older children is high, with only about 20% surviving for more than five years.
Scientists at The Institute of Cancer Research, London, worked with colleagues from the Hopp Children’s Cancer Centre Heidelberg in Germany, the UCL Great Ormond Street Institute of Child Health, London, and St Jude Children’s Research Hospital, USA, to carry out a large-scale study of 241 infants from around the world with glioma brain tumours.
Writing in Cancer Discovery, they found that 54% (130) of the tumour samples had a different genetic make-up from other forms of childhood brain tumours, despite looking similar under the microscope.
Of these, 65 had specific molecular weaknesses, including ALK and NTRK gene fusions, which can be targeted with existing precision medicines.
When the research team looked at mice with brain tumours caused by ALK gene fusions, they found that that lorlatinib significantly shrunk tumours in seven out of eight mice (88%), while tumours in mice given chemotherapy kept growing, albeit at a slower rate.
They also grew three-dimensional ‘mini tumours’ from patient samples and found those that had fusions of NTRK with other genes were particularly sensitive to drugs blocking NTRK: tumours with these fusion mutations were between two and nine times more sensitive to the targeted treatments entrectinib, crizotinib and milciclib than those without.
Clinical trials are now due to begin to test the benefit of targeted drugs blocking the ALK and NTRK gene fusions in infant brain tumours – and to better understand the biology of tumours which don’t have these faults.
Professor Chris Jones, professor of paediatric brain tumour biology at The Institute of Cancer Research, London, said: “Our study offers the biological evidence to pick out those infants who are likely to have a better outcome from their disease, so these very small children and their families can be spared the harmful effects of chemotherapy.
“We showed that brain tumours in infants have particular genetic weaknesses that could be targeted with existing drugs – and clinical trials are planned to test the benefit of these precision medicines as a first-line treatment in clinical trials as soon as possible.”
Dr Matthew Clarke, clinical research fellow in the glioma team at The Institute of Cancer Research, London, added: “Chemotherapy is currently a good treatment option for babies with brain tumours – but our study has found that some children could be spared this treatment. With further testing, I’m hopeful that existing targeted drugs could expand our arsenal of options to treat these smallest of patients.”
Infant high grade gliomas comprise multiple subgroups characterized by novel targetable gene fusions and favorable outcomes. Cancer Discovery 1 April 2020
https://cancerdiscovery.aacrjournals.org/content/early/2020/03/25/2159-8290.CD-19-1030
Leave a Reply