Project description
Revealing non-genetic determinants of cancer cell plasticity in gene-related cancers
The ability of cancer cells to change their molecular and phenotypic identities contributes to metastases and treatment resistance. Stopping or reversing this could open a new pathway to cancer treatment. Paediatric tumours exhibit remarkable plasticity. Using organoid technology, single-cell genomics and lineage tracing approaches, the consortium of the ERC-funded MaturingKidsCancer project recently showed that paediatric cancers exhibit robust yet pharmacologically reversible plasticity at the level of the epigenome. MaturingKidsCancer will use single-cell transcriptomics and epigenomics, its unique paediatric cancer organoids and patient-derived tissues to uncover fundamental principles governing cancer cell plasticity. Outcomes will support new methods and strategies for cancer therapy.
Objective
Introduction
Cancer cell plasticity, the ability of cancer cells to change their identity, enables tumors to adapt to hostile environments, aiding metastasis and resistance to treatments. Hence, plasticity is a major unsolved problem frustrating effective treatment. Unraveling the mechanisms underlying cancer cell plasticity is crucial to establish new avenues for cancer therapy. In contrast to adult cancers, many pediatric tumors are driven by a single genetic alteration that fuels their aggressive nature through remarkable plasticity. Despite their differences, pediatric cancers offer a unique platform to investigate cancer cell plasticity due to their genetically clear characteristics. I hypothesize that plasticity can be reversed to differentiate tumor cells and “mature cancer”.
Goal
Building upon previous ERC-StG funding, we have successfully utilized organoid technology, single-cell genomics, and lineage tracing approaches to uncover the origins of various pediatric cancers. Our findings revealed that these cancers exhibit robust yet pharmacologically reversible plasticity at the level of the epigenome. The goal of this proposal is to reverse cell state changes during tumorigenesis to “mature cancer”.
Approach
We will I) apply advanced (spatial) single-cell transcriptomics and epigenomics approaches to a unique cohort of pediatric tumors and metastases to map out cell state changes during disease progression, II) utilize our unique pediatric cancer organoids to interrogate and target hierarchical trajectories with the aim to mature cancer, and III) screen the enhancer-ome to identify non-genetic determinants of cancer cell plasticity.
Innovation
Integrating these cutting-edge technologies on patient-derived tissues and organoids will uncover fundamental principles governing cancer cell plasticity. The research will pioneer innovative methodologies and reveal strategies for identifying cancer maturation targets, advancing cancer therapy research
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
- natural sciences biological sciences genetics epigenetics epigenomes
- engineering and technology environmental engineering energy and fuels
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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)
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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.
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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-ERC - HORIZON ERC Grants
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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) ERC-2024-COG
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3584CS Utrecht
Netherlands
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