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Innovative metabolic mapping to predict and enhance the response of targeted anti-cancer therapies

Lead Research Organisation: Institute of Cancer Research
Department Name: Division of Cancer Biology

Abstract

Evidence suggests that the way cells consume and process nutrients, collectively known as metabolism, differs between healthy and tumour cells and can even change the way they communicate with adjacent cells, grow, and importantly, respond to therapy. Nutrient availability in the environment where the tumour is growing can also have a fundamental impact on the effectiveness of anti-cancer therapies. This project will draw on the strengths of innovative tools and methods to track the metabolism of breast cancer tumours and pre-clinical models, and identify the metabolic determinants that guide the response to anti-cancer therapies. In this context, it will assist with gaining insight into how certain drugs affect tumour metabolism, and ultimately, how the metabolism of a tumour and its surrounding affect its response to therapy. In the longer term this knowledge will expose weaknesses in the tumour's armour and unveil more effective therapeutic strategies where diet and metabolic targets could help circumvent drug resistance and slow down tumour growth.

Publications

10 25 50
 
Description This award has propelled several studies interrogating how metabolism influences different stages of tumour biology with the goal to improve cancer disease management and treatment in the clinic. These include
• A study highlighting the role of dietary omega 6/3 fats and aspirin in regulating the growth of tumours driven by PIK3CA mutation.
• A study connecting BRCA1 deficiency with differential metabolic rewiring in glutamine metabolism exposing a metabolic vulnerability of BRCA1 mutant breast cancers.
• A study involving pan-cancer flux balance analysis which represents an innovative approach that involves genome-wide prediction of gene essentiality and metabolic flux changes from transcriptomics data, allowing for specific metabolic pathways and targets to be identified in subgroups of patients.
Exploitation Route The implications for these findings are significant both in the context of furthering our scientific understanding of this field but also for potentially identifying novel therapeutic targets for management of cancer-related growth. I will soon be seeking for further funding with collaborators from Royal Marsden Hospital to run a clinical trial assessing the effect of dietary intervention with/without aspirin treatment in PI3K-induced oncogenicity.
Sectors Education

Pharmaceuticals and Medical Biotechnology

 
Description Tracking metabolic reprogramming through stable isotope-resolved metabolomics
Amount £497,353 (GBP)
Funding ID MC_PC_ MR/X013715/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 02/2023 
End 03/2023