Brain Tumour in Children Project. New treatments for diffuse midline gliomas



A new type of drug that targets a particular protein could become the first ever treatment designed for children with diffuse midline gliomas (formerly known as DIPG)


Diffuse midline glioma is a type of primary, high-grade brain tumour that occurs in children. It is one of the most fatal paediatric brain tumours, with less than 1% of patients diagnosed surviving more than 5 years.

The dismal prognosis of these tumours can be blamed on its location within the brain, the brain stem. This part of the brain is responsible for a number of critical bodily functions including breathing, sleeping and heartbeat, meaning surgery is not an option.

The current standard of care to treat diffuse midline glioma is radiation therapy. However, this is not a cure and only reduces the symptoms temporarily, making new and effective treatments for this tumour type critical.

Scientists at The Institute of Cancer Research, London, in collaboration with international colleagues led a study to find drugs that could specifically target diffuse midline gliomas.

Previous research discovered that a particular enzyme (a type of protein) called ACVR1 is altered in approximately 25% of diffuse midline gliomas. These alterations cause ACVR1 to become overactive, which leads to excessive cell proliferation and tumour growth.

Interestingly, changes to ACVR1 haven’t been found in any other type of cancer, but they do cause a rare inherited disease, sometimes called “stone man syndrome” because it causes damaged muscle to be replaced with bone.

Following this discovery, research teams including the Structural Genomics Consortium in Oxford and at The Institute of Cancer Research have been working hard to find drugs that could target the altered ACVR1 enzyme.

A recent study published in Communications Biology tested 11 drugs that had the ability to block the activity of the ACVR1 enzyme. From these 11 drugs they found two potential drugs that were effective at killing the tumour cells while having very little effect on healthy brain cells.

The research team then tested these two drugs in pre-clinical models of diffuse midline gliomas and found that the drugs were able to cross the blood brain barrier and prevent tumour growth.

Professor Chris Jones, lead researcher of this study said: “It’s simply not good enough that we can cure some cancers, but in others we have seen no progress in decades. We owe it to children and their families to do better.

“My lab discovered that mutations in the ACVR1 gene occur in a quarter of diffuse midline gliomas and it’s incredibly exciting to see this now lead to potential new drugs for the disease. I can’t wait to see how they perform in patients.”

The two potential drugs are now being further developed by a company called M4K Pharma, which aims to discover and develop affordable drugs for rare childhood diseases.