Researchers are launching the GUARD-CH programme, a £1.25 million international research initiative backed by Cancer Research UK and the Canadian Cancer Society, to investigate whether GLP-1 receptor agonists can prevent the progression of clonal haematopoiesis and associated blood cancers. Co-led by Professor Philip Awadalla at Oxford Population Health and the University of Oxford’s Big Data Institute alongside Professor Stephanie Xie at the Princess Margaret Cancer Centre in Toronto, the study aims to determine if widely prescribed diabetes and obesity medications can disrupt inflammatory pathways that drive mutant blood stem cell expansion.
GUARD-CH Programme Targets Clonal Haematopoiesis Risks
Clonal haematopoiesis is an age-related condition where blood-forming stem cells carrying acquired mutations multiply faster than normal cells. While not cancer itself, clonal haematopoiesis significantly raises the risk of developing acute myeloid leukaemia and myelodysplastic syndromes, alongside contributing to stroke, cardiovascular disease, and other chronic illnesses through systemic inflammation.
The Biological Mechanism of Inflammatory Memory in Blood Stem Cells
The research builds directly on findings published in the journal Nature (2026;655(8122):458-467) titled “Human haematopoietic stem cells remember inflammatory stress,” authored by Zeng AGX, Nagree MS, Jakobsen NA, and colleagues. The study uncovered a distinct subset of human blood stem cells that retains a durable molecular memory of past inflammatory exposure. Professor Awadalla explains that inflammatory and metabolic stresses—such as obesity, diabetes, poor diets, and air pollution—create conditions favoring the growth of these mutant stem cells. The team’s population-level analyses linked a stronger inflammatory memory signature directly to higher risks of clonal haematopoiesis or death from various causes.
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Testing Semaglutide and GLP-1 Therapies in Clinical Studies
The newly funded GUARD-CH programme will test whether GLP-1 receptor agonists like semaglutide can reduce inflammation and strip away the competitive advantage held by mutant blood stem cells. “The ultimate goal is to establish whether an existing and widely prescribed class of medicines could be used to prevent blood cancers and other diseases in people with clonal haematopoiesis,” according to Professor Awadalla. Oxford Population Health will manage the population-scale and computational components, leveraging expertise in genomics, molecular epidemiology, and multimodal data integration.
Developing Practical Blood Tests for Patient Monitoring
Researchers collaborating on the initiative will also develop a practical blood test capable of measuring specific disease markers to identify individuals who stand to benefit most from the intervention. This diagnostic tool will undergo evaluation during a prospective study across Canada and the UK in partnership with Perspectum. The study will track patients diagnosed with clonal haematopoiesis and metabolic disease for a duration of up to four years, generating the clinical and biological evidence required to design a future randomized cancer prevention clinical trial.
Frequently Asked Questions
What is clonal haematopoiesis?
Clonal haematopoiesis is an age-related condition where blood-forming stem cells with acquired genetic mutations expand at a faster rate than healthy stem cells, increasing the risk of blood cancers and cardiovascular disease.
How do GLP-1 receptor agonists relate to this research?
GLP-1 receptor agonists, commonly used for diabetes and obesity, are being investigated by the GUARD-CH programme to see if they can reduce inflammation and disrupt the molecular memory that drives mutant stem cell expansion.
Who is funding the GUARD-CH programme?
The £1.25 million research initiative is co-funded by Cancer Research UK and the Canadian Cancer Society.
How long will the clinical evaluation take?
The prospective study in Canada and the UK, conducted in partnership with Perspectum, will follow patients with clonal haematopoiesis and metabolic disease for up to four years.
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