Objective
Metastasis is responsible for over 90% of deaths that occur in patients with cancer. So far there are no therapies that precisely target a metastatic disease due to the limited number of efficient druggable targets.
Recently, I discovered in melanoma: circulating tumor cells are depending on arginine for their survival. In addition, I revealed that liver metastases specifically upregulate their alanine metabolism during metastasis. Thus, metastatic cells at different stages have dependencies on unique amino acids (AA). While most research focuses on the primary stage, my proposal will focus on the missing gap aiming to prevent metastases formation. Based on these new paradigm-changing discoveries, I hypothesize that metastatic cells modulate their AA metabolism during metastatic progression, and targeting the unique AA dependencies will decrease their survival and metastatic potential. Using sophisticated in vivo metastasis assays both in mouse and in patient, cutting-edge mass spectrometry and in vivo isotope tracing technologies, I will identify metastasis-specific inhibitors by investigating the following questions. I. How does arginine support melanoma cell survival in circulation? By using metabolomics, stable isotope tracer analysis and transplantation assays both in mouse and human, I will uncover how we can use this unique AA dependency of CTCs as a novel target. II.How does metabolic heterogeneity in the circulating tumor cells support organotropism? To mechanically dissect metastatic organotropism, I will map metabolic differences in melanoma metastases and also examine how we can target alanine metabolism to block metastases.
The understanding of AA adaptation of cancer cells is essential for the prevention of metastasis. My results will reveal new metabolic pathways that are required by metastasizing cells in vivo and therefore will fundamentally advance the ability to develop new targeted therapies for preventing early and late-stage metastatic cancer.
Fields of science (EuroSciVoc)
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.
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.
- medical and health sciences clinical medicine oncology skin cancer melanoma
- medical and health sciences medical biotechnology cells technologies
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Keywords
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.1.1 - European Research Council (ERC)
MAIN PROGRAMME
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Topic(s)
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.
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
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.
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-ERC - HORIZON ERC Grants
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2022-STG
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
45147 Essen
Germany
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.