Cholesterol inhibitors for diffuse midline glioma

Diffuse midline glioma (DMG) is a childhood brain tumour that is currently incurable; average survival is 9-12 months, and children rarely survive more than 2 years after diagnosis. Novel treatments are desperately needed which are based on the unique biology of these tumours.

Project Details

  • Project Title

    Combined targeting of ACVR1 and cholesterol metabolism in diffuse midline glioma

  • Lead Researcher

    Professor Chris Jones

  • Research Centre

    Institute of Cancer Research

  • City & Institution Postcode

    Surrey, SM2 5NG

  • Start Date

    1 August 2023

  • Duration

    36 months

  • Grant Amount


Chris Jones researcher 1 scaled


Professor Chris Jones and his team discovered faults in the gene ACVR1 to be present in DMG, and have been working to take specific drugs targeting ACVR1 to clinical trial. Although promising, they are likely to produce only modest benefits on their own, and the team have been looking to combine them with other drugs which may be more likely to produce a durable response in patients.

Recently, the team discovered a previously unknown link between the ACVR1 gene and cholesterol metabolism to be a possible Achilles heel in DMG. Treating these tumour cells with ACVR1 inhibitors as well as drugs which interfere with production or transport of cholesterol led to a greater effect than you would expect by adding the effects of them alone. These include commonly used anti-cholesterol drugs such as statins, which gives us the exciting potential for moving rapidly to the clinic. To achieve this, Professor Jones plans a research programme that will help unravel why DMG cells are dependent on cholesterol, and how inhibiting ACVR1 subsequently kills those cells. This will be done by cutting edge molecular analyses in disease models established from patient tumour samples. The project will also look at a large number of different ACVR1 and cholesterol inhibitors in a wide panel of these cells to pick the best combination, and test this in mouse DMG models.


What difference will this project make?

As cholesterol-targeting drugs such as statins are readily available and non-toxic, this project has the possibility of moving this treatment quickly to clinical trial, including in the UK, via the teams leadership role in the international CONNECT consortium. These tumours have been highlighted in multiple petitions to the UK Parliament as representing a major unmet need, and any new treatment has the potential to make a major impact for children with this terrible disease.

About the Research Team

Professor Chris Jones is an international expert in the biology of childhood glioma such as DMG, and runs a lab focused on developing new treatments for these tumours at the Institute of Cancer Research in London, one of the world’s leading research institutes. Chris is also a leader in several international clinical trials networks and is the biology reference laboratory for national clinical trials within the UK.                                             

Dr Rebecca Rogers is an experienced laboratory researcher in the Jones Lab and has made the exciting initial discoveries upon which this project is based. Dr Rodgers is ideally suited to supervise this work as part of her career development to an eventual independent researcher in the field of childhood brain tumours.

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