Project description
How ageing fuels metastasis
As we age, our metabolism and tissue microenvironment undergo profound changes that alter how cells respond to stress and disease. These age-related metabolic shifts can influence cancer progression, particularly the spread of tumours to distant organs. Since metastasis remains the leading cause of cancer mortality, understanding how ageing promotes this process is essential. With the support of the Marie Skłodowska-Curie Actions programme, the PrimeAge project will explore how tumour-secreted factors induce age-dependent metabolic nutrient priming in distant organs, fostering metastasis formation. Using melanoma as a model, the project will combine spatial metabolomics and multi-omics analyses to identify and target age-specific metabolic pathways, paving the way for personalised anti-metastatic interventions.
Objective
Metastasis is the leading cause of death in cancer patients. Aging is an important risk factor for metastasis formation, yet the underlying processes remain poorly understood. Given the increase in aging populations worldwide, elucidating mechanisms of age-promoted metastasis formation is an important and timely topic addressed in this proposal. Recently, the Fendt group has pioneered the concept that tumor-secreted factors (TSF) induce nutrient priming of distant organs for metastasis formation. This concept is exemplified by adaptations in lipid metabolism of target organs, triggering a pro-metastatic signaling pathway in invading tumor cells. I propose that nutrient priming is age-dependent, as the metabolism changes with age, contributing to the enhanced risk of metastasis formation in the elderly. I will investigate this concept using melanoma as a prototypic cancer of age-dependent, aggressive metastatic behavior. I will address 3 specific objectives: (1) Identify age-dependent metabolic response of distant organs to TSF using mass spectrometry imaging-based spatial metabolomics in young and aging mouse models, and corroborate my findings in melanoma patients. (2) Elucidate molecular mechanisms whereby identified metabolites promote the pre-metastatic potential of the distant niche by applying genetic screens as well as multi-omics and functional assays to spheroid models of metastasis. (3) Validate the therapeutic potential of intercepting age-specific metabolic priming using pharmacological and genetic perturbations in mouse melanoma models. Ultimately, I expect to identify age-specific metabolic adaptations in pre-metastatic niches and to document that these pathways provide targets for personalized therapy of metastatic tumors in the elderly. This ambitious proposal is based on my expertise in elucidating the instructive role of metabolites in cell fate and function, and on expert skills in cancer metabolism research that I will acquire in the Fendt lab.
Fields of science (EuroSciVoc)
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CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
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Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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Topic(s)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) HORIZON-MSCA-2023-PF-01
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9052 ZWIJNAARDE - GENT
Belgium
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