Project description
Decoding colorectal cancer metastasis
Colorectal cancer is the second leading cause of cancer-related deaths worldwide, with common metastatic spread to the liver and lungs. Effective therapies to prevent this progression are lacking, partly due to limited understanding of how cancer cells disseminate and establish distant tumours. The ERC-funded META-CYCLE project will study the metastatic cascade through a systems biology approach. Researchers will perform multi-omics analysis to identify specific drivers of invasion seeding and outgrowth. They will also investigate the role of the liver microenvironment and endothelial cells in promoting metastasis. Project findings will provide a comprehensive picture of metastatic colorectal cancer, paving the way for novel therapeutic strategies to limit disease progression.
Objective
Colorectal cancer (CRC) is the second leading cause of cancer-related mortality worldwide, accounting for
nearly 10% of cancer-related deaths. The majority of CRC-related deaths result from metastatic
dissemination, with the liver and lung being the most frequent distant sites of metastasis. Effective therapies
to prevent metastatic CRC progression are lacking. This gap stems from our limited understanding of the
cancer-intrinsic and tumor microenvironmental factors that drive advancement through each intermediate
step of the metastatic cascade.
Here, we will use systems approaches to unravel the life cycle of metastatic cells, focusing on cancer cell
plasticity and interactions with host tissues. First, we will use in vivo CRISPR screening to identify drivers
of invasion, dissemination, seeding, and outgrowth. This approach will be complemented by single-cell
multi-omics analyses to uncover the regulatory networks governing these processes. Next, we will explore
the dynamics of the liver pre-metastatic niche using single-cell RNA sequencing, proximity labeling, and
immunofluorescence to dissect its metastasis-promoting cellular networks and gradual reversal after primary
tumor ablation. Finally, we will identify host factors that regulate metastatic extravasation and vessel co-
option by functionally investigating the role of liver endothelial cells throughout metastatic progression.
This will be achieved through a combination of in vivo interaction screening, in vitro models, and
comparison to spatial transcriptomic datasets from patient samples.
By integrating these complementary approaches, our study aims to provide a comprehensive understanding
of the key drivers and modulators of metastatic CRC. These insights could pave the way for the development
of novel therapeutic strategies aimed at preventing or limiting metastatic disease progression in CRC
patients.
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.
- social sciences sociology demography mortality
- medical and health sciences clinical medicine oncology
- natural sciences biological sciences genetics RNA
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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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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
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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-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.
8092 Zuerich
Switzerland
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.