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Mair Group

Metabolic phenotypes in cancer

Research summary

My group explores how brain cancers use nutrients to survive and grow. We hope to identify cancer-specific metabolic vulnerabilities that can be targeted, therapeutically, to improve prognosis. We are particularly interested in how certain brain cancers transform from a slow growing low-grade cancer to a rapidly expanding high-grade cancer and how nutrient metabolism may promote this.

Introduction

My group is interested in how metabolic flux is altered in cancer and how heterogeneity in the resultant phenotypes affect cell state transition and treatment response.

As a clinically active neurosurgeon my group use patient samples to generate models of brain cancer to probe the effects of cell and microenvironmental perturbation on cancer metabolism and the immune environment.

As principal investigator on several clinical trials, my group complements our bench approach through clinical validation as well as by using our large human biobank to further probe the landscape of brain cancer.

Dr Richard Mair

Independent Clinical Fellow

Research programmes

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Low to high grade transformation in IDH mutant glioma

Mutation in isocitrate dehydrogenase (a metabolically active enzyme) is associated with a subset of primary brain cancers – termed astrocytoma and oligodendroglioma. These IDH-mutant gliomas tend to occur in patients under 40 and present at a low grade. Despite an initial indolent phase, these tumours inexorably transform to a higher grade at which point they rapidly progress. These tumours possess a characteristic metabolic phenotype as IDH mutation leads to neomorphic enzymatic activity and the production of 2-hydroxyglutarate (2-HG), an oncometabolite. This metabolite has pleotropic cellular effects, many of which have not been explored in great depth. We are interested how this metabolic phenotype affects both high grade transformation and treatment response.

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Cell intrinsic metabolic phenotypes in glioblastoma

We recently demonstrated the presence of cell intrinsic metabolic phenotypes in glioblastoma that influence therapeutic efficacy. Our study showed that these phenotypes may possess different sensitivity to therapy and that they exist at scales that are imageable with current metabolic imaging techniques. My group are working to identify whether this paradigm is useful for individualising treatment for glioma patients.

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Minderoo Precision Brain Tumour Programme & 5G Adaptive Precision Trial

In this programme we recruit patients with primary brain cancer for ‘real time’ whole genome and transcriptome sequencing to identify whether we can use these data to better inform treatments. This led to the recent launch of the 5G clinical trial (via a collaboration with Dr Juanita Lopez at the Royal Marsden Hospital) which is the world’s first adaptive precision platform trial for glioma.

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