Objective
Anticancer therapy is >70 years old, and nucleotides are the oldest target in cancer treatment. Despite its long history, this treatment suffers high rates of resistance and toxicity. What are the reasons? A cell can gain nucleotides via de novo synthesis (DNS) or from salvage pathways. DNS inhibition can be bypassed by nucleotides produced by surrounding cells or distant organs, causing resistance. Cancer cells were traditionally studied in isolation, with (bulk) techniques precluding identification of cell type-specific targets, causing toxicity. To date, the cellular sources of nucleotides in healthy and tumor tissues are poorly characterized. Can the complexity of metabolic crosstalk in tissues be captured by the traditional means? I hypothesize that cancer and stromal cells differ in how they utilize nucleic acid building blocks from external and internal sources. A single cell resolution is needed to disentangle their interactions, and inhibition of both DNS and cancer-specific salvage is required for a successful blockade. I aim to define the nucleotide sources in heathy tissues and tumors, characterize their adaptations to DNS blockade to uncover the network of metabolic interactions in tissues and find effective and specific combinations of targets. To reach this goal, I will use a unique combination of single cell multi-omics and tailored mouse models, an expertise and tools that I took the lead to set up. I will selectively disable DNS in the stroma (host mouse) and in cancer cells (syngeneic lung tumors) to generate tumors dependent on internally or externally produced nucleotides. In an integrative approach using spatial and single cell transcriptomics & metabolomics in situ, and functional genetic screen, I will search for targetable metabolic vulnerabilities of DNS-disabled cancer cells. This innovative research opens the path to understanding the organization of tissue metabolic homeostasis for new personalized metabolism-based anticancer medicine.
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.
- humanities history and archaeology history
- medical and health sciences clinical medicine oncology
- natural sciences biological sciences genetics nucleotides
- medical and health sciences basic medicine physiology homeostasis
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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)
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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
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-2021-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.
252 50 Vestec
Czechia
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.