Artificial Intelligence used to identify new drug combination for children with incurable brain cancer

Scientists at The Royal Marsden NHS Foundation Trust and the Institute of Cancer Research (ICR) used artificial intelligence-enhanced tools to successfully propose a new combination of drugs for use against an incurable childhood brain cancer.

Dr Fernando Carceller

The approach, which is designed to expand researchers’ capabilities using AI, allowed our scientists to explore ideas on how to target children with diffuse intrinsic pontine glioma (DIPG) who have mutations in a gene called ACVR1.

It was found that using a drug called everolimus alongside a another called vandetanib could enhance vandetanib's capacity to pass through the blood-brain barrier in order to treat the cancer. The proposed combination has proved effective when tested in the lab and has already been tested in a small cohort of children.

The study, led by The Royal Marsden and ICR, is an example of how use of an AI-augmented approach can open up new doors for cancer treatment by spotting new ways of combining existing medicines.

The initial plan for the research, published in the journal Cancer Discovery, came from BenevolentAI – a company that has built an AI drug discovery platform.

A quarter of children with DIPG have a mutation in a gene known as ACVR1, but there is currently no treatment targeting this mutation approved for use in DIPG.

The targeted drug vandetanib, which is approved for treating thyroid cancer, acts against the ACVR1 gene, but has difficulty getting past the blood brain barrier. It is pushed back out of the brain, meaning it cannot build up to a high enough concentration in the brain to have a therapeutic effect.

The drugs identified in the study, vandetanib and everolimus, are already approved to treat other types of cancer by NICE, the European Medical Association (EMA) and the US Food and Drug Administration (FDA), and could be repurposed for use in combination to treat children with DIPG and an ACVR1 mutation.

In the study, doctors also carried out initial tests of the drug combination in four DIPG patients.

The next step will be for the drug combination to enter clinical trials, which researchers hope will happen in the near future.

Dr Fernando Carceller, Consultant in Paediatric and Adolescent Neuro-Oncology, in the Oak Paediatric and Adolescent Drug Development Unit at The Royal Marsden and Leader of the Paediatric and Adolescent Neuro-Oncology and Drug Development team at the ICR, said:

“This encouraging research highlights the possibilities of harnessing Artificial Intelligence to find better cures for childhood cancers.

“Close collaboration between clinicians at The Royal Marsden and scientists at the ICR made possible this bench-to-bedside approach. The clinical results are too preliminary as to draw firm conclusions, but we are working to take this combination forward in a clinical trial for children with ACVR1-mutant DIPG.”

Professor Chris Jones, Professor of Paediatric Brain Tumour Biology at the ICR, said:

“DIPG is a rare and aggressive childhood brain cancer, and survival rates have not changed over the past 50 years, so we desperately need to find new treatments for this disease.

“Our study demonstrates just how much AI can bring to drug discovery for cancers like DIPG, in proposing new treatment combinations that would not have been obvious to people.

“We still need a full-scale clinical trial to assess whether the treatment can benefit children, but we’ve moved to this stage much more quickly than would ever have been possible without the help of AI.”

The Oak Paediatric and Adolescent Drug Development Unit is funded by The Royal Marsden Cancer Charity. Dr Fernando Carceller is part funded by a generous donation from George and the Giant Pledge to The Royal Marsden Cancer Charity. To learn more about ways you can support The Royal Marsden Cancer Charity, please visit their website.