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.
People |
ORCID iD |
| George Poulogiannis (Principal Investigator / Fellow) |
Publications
Leslie TK
(2024)
A novel Nav1.5-dependent feedback mechanism driving glycolytic acidification in breast cancer metastasis.
in Oncogene
Tripp A
(2022)
Banking on metabolomics for novel therapies in TNBC
in Cell Research
Dannhorn A
(2024)
Morphological and molecular preservation through universal preparation of fresh-frozen tissue samples for multimodal imaging workflows.
in Nature protocols
Kaufmann M
(2024)
Testing of rapid evaporative mass spectrometry for histological tissue classification and molecular diagnostics in a multi-site study
in British Journal of Cancer
Karalis T
(2024)
The Emerging Role of LPA as an Oncometabolite.
in Cells
Ling S
(2025)
Use of metabolic imaging to monitor heterogeneity of tumour response following therapeutic mTORC1/2 pathway inhibition.
in Disease models & mechanisms
Goodwin R
(2025)
Visualizing Cancer Heterogeneity at the Molecular and Cellular Levels: Lessons from Rosetta
in Cancer Discovery
Kreuzaler P
(2023)
Vitamin B5 supports MYC oncogenic metabolism and tumor progression in breast cancer.
in Nature metabolism
| 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 |