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AI identifies possible drug combination for brain cancer

Thursday September 23rd 2021

Artificial intelligence-enhanced tools have been used to identify a new combination of drugs that could treat a rare and incurable childhood brain cancer.

Scientists, led The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust, found everolimus with vandetanib was a promising treatment for children with diffuse intrinsic pontine glioma (DIPG) who have mutations in the ACVR1 gene.

When tested in mice – and in a small group of children – the combination enhanced vandetanib's capacity to pass through the blood-brain barrier to treat the cancer.

Writing in Cancer Discovery, the research team say their findings are an example of how an AI-augmented approach can open up new doors for cancer treatment.

A quarter of children with DIPG have an ACVR1 mutation, but there is no treatment targeting this mutation approved for use in DIPG.

Vandetanib, which is approved for treating thyroid cancer, acts against the ACVR1 gene, but it is unable to get past the blood brain barrier and because it is pushed back out of the brain, it cannot build up to a high enough concentration in the brain to have a therapeutic effect.

Using an AI platform created by BenevolentAI to identify drugs that could be used to target ACVR1 mutations in DIPG, the combination of vandetanib with everolimus, which prevents vandetanib from being ejected from the brain, was suggested following analysis by the computational tool.

The ICR team showed that combining the two drugs increased the amount of vandetanib in the brains of mice with DIPG by 56% and that the treatment extended survival in mice by 14% compared with those receiving a control treatment.

Initial tests of the drug combination were undertaken in four DIPG patients and the next step is for clinical trials to begin.

Professor Chris Jones, professor of paediatric brain tumour biology at The Institute of Cancer Research, London, 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.

“The AI system suggested using a combination of two existing drugs to treat some children with DIPG – one to target the ACVR1 mutation, and the other to sneak the first past the blood brain barrier. The treatment extended survival when we tested it in a mouse model, and we have already started testing it out in a small number of children.

“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.”

Professor Kristian Helin, chief executive of The Institute of Cancer Research, London, added: “In this study, use of AI has identified a drug combination which appears to have promise as a future treatment for some children with incurable brain cancer. It’s exciting to think that it could become one of the first examples of a treatment proposed by AI going on to benefit patients.”

Cancer Discovery 23 September 2021

Tags: Brain & Neurology | Cancer | Pharmaceuticals | UK News

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