Project description
Targeting the Achilles heel of cancer
Cancer cells often present with an imbalanced number of chromosomes or chromosomal translocations. Despite extensive research into the origin of aneuploidy, its underlying mechanisms have not been fully elucidated. The EU-funded CancerAneuploidy project aims to study the cellular consequences of aneuploidy. To achieve this, scientists will use state-of-the-art genomic approaches and chemical perturbation and investigate the evolution of aneuploidy in tumours. The discovery of the vulnerabilities caused by aneuploidy has the potential to be exploited for killing cancer cells. Collectively, the project's results will shed light on the biological enigma of aneuploidy and offer new opportunities for cancer therapy.
Objective
Aneuploidy, an imbalanced number of chromosomes or chromosome arms, is a distinct feature of cancer. Recent years have seen conceptual, methodological and technical advances in the field of cancer aneuploidy research, but we are just beginning to scratch the surface of the underlying biology, and the potential vulnerabilities of aneuploid cancer cells remain under-explored. Cancer aneuploidy is therefore a biological enigma and a missed opportunity for cancer therapy.
Identifying the “Achilles heels” of aneuploidy remains a holy grail of cancer research. However, current models of aneuploidy fail to fully recapitulate the cellular consequences of aneuploidy in cancer, thus compromising the identification of aneuploidy-induced cellular vulnerabilities. The time is ripe to tackle cancer aneuploidy with state-of-the-art genomic and functional approaches.
In this project, I propose to address the following key questions:
1) What forces shape the evolution of aneuploidy in tumors? We will integrate in silico analyses of clinical data, in vitro modeling in isogenic human cell lines, and in vivo experiments in mice, to elucidate how various cellular contexts shape the tumor aneuploidy landscape.
2) What cellular vulnerabilities are induced by aneuploidy? We will combine isogenic cell lines with large-scale genetic and chemical perturbation screens, in order to identify, validate, and mechanistically dissect vulnerabilities induced by aneuploidy in human cancer cells.
These research aims fall well within my unique expertise. I mapped various aneuploidy landscapes and developed innovative experimental and computational tools for studying cancer aneuploidy.
A successful completion of the project will shed light on the context-dependent cellular consequences of aneuploidy in cancer and provide proof-of-concept for its potential targeting. Ultimately, identifying aneuploidy-specific vulnerabilities will pave the way for the therapeutic exploitation of this hallmark of 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
- natural sciences biological sciences genetics chromosomes
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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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H2020-EU.1.1. - EXCELLENT SCIENCE - 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.
ERC-STG - Starting Grant
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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-2020-STG
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69978 Tel Aviv
Israel
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