Objective
Cancer genomes are riddled by remarkably complex forms of structural variants collectively known as complex genomic rearrangements (CGRs). Our previous work showed that CGRs occur at high frequency in some of the deadliest cancers in humans and underpin drug resistance and poor prognosis. Yet, the impact of CGRs on immune escape, cancer cell plasticity, metastasis, drug resistance and clonal evolution remains elusive. As a result, we have not been able to deliver eagerly awaited breakthroughs for the treatment of tumours driven by CGRs.
In this ERC project, I aim to change the paradigm for cancer therapy development for tumours driven by CGRs. To this aim, BrokenChromosomes will first rely on a multi-disciplinary approach combining spatially resolved multi-omic profiling of tumours to elucidate the mechanisms whereby CGRs shape the tumour-immune microenvironment to achieve immune escape and modulate cancer cell fitness and plasticity during tumour evolution and metastatic spread, which might open new therapeutic avenues to treat currently incurable cancers driven by CGRs. Second, we will study the differentiation dynamics and phenotypes of neoantigen-specific tumour-infiltrating T cells in tumours showing high rates of CGRs, and we will assess their tumour-killing activity using patient-derived ex vivo tumour-immune co-cultures. By assessing the immunogenicity of diverse mutations in tumours driven by CGRs, I aim to provide critical new knowledge to enable the development of therapeutic breakthroughs for these tumours using immunotherapies. Finally, we will decode the interplay between epigenetic dysregulation at centromeres, chromosomal instability and CGR formation, which might also have far-reaching implications beyond cancer by explaining why e.g. increased rates of aneuploidy in healthy cells, e.g. oocytes, is an age-dependent process.
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 basic medicine pharmacology and pharmacy drug resistance
- natural sciences biological sciences genetics mutation
- medical and health sciences clinical medicine oncology
- medical and health sciences basic medicine immunology immunotherapy
- natural sciences biological sciences genetics genomes
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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-2025-COG
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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.
OX1 2JD Oxford
United Kingdom
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.