Project description
Improving colorectal cancer liver metastasis treatments
Between 25 % and 50 % of colorectal cancer patients develop liver metastases through tumour vessel co-option, a process that bypasses the formation of new blood vessels. This is resistant to standard anti-angiogenic therapies. Lymphoid Enhancer Binding Factor 1 (LEF1) may regulate gene expression that supports tumour cell survival. Supported by the Marie Skłodowska-Curie Actions programme, the UNMET project will investigate whether blocking LEF1 can inhibit Wnt signalling in vessel-co-opted tumours, with the goal of improving treatment. It will use patient-derived organoids and advanced microscopy to study tumour characteristics and enhance the delivery of anti-angiogenic therapies (AAT). It will also identify diagnostic markers through blood tests and CT scans, leveraging AI to more effectively predict treatment responses.
Objective
An estimated 25-50% of colorectal cancer patients will encounter liver metastasis during their illness. Tumor vessel co-option is a non-angiogenic mechanism whereby tumors, rather than forming new blood vessels (a process known as angiogenic growth), hijack pre-existing blood vessels in the affected organ. Standard anti-angiogenic therapy (AAT) is ineffective against vessel co-optioned tumors. This process has been linked to unfavorable patient outcomes. The exact mechanisms distinguishing vessel co-option remain elusive. Preliminary data suggest that metastatic cancer displaying the vessel co-option phenotype increased in gene expression, regulated by Lymphoid enhancer binding factor 1 or LEF1 protein, which is a key mediator of the Wnt/-catenin signaling. The dysregulation of the Wnt pathway can activate target genes that promote cell proliferation and survival. In this proposal, I hypothesize, that inhibition of the Wnt signaling (e.g. by blocking LEF1), will change the properties of vessel co-optioned tumors and improve the effectiveness of conventional treatment for liver metastases. Patient-derived organoids, obtained from hospitals, will be used to validate whether the inhibition of LEF1 will impact the vessel co-option phenotype, making it more susceptible to AAT. Advanced microscopy techniques, like Atomic force microscopy and Scanning ion-conductance microscopy, will facilitate monitoring the decreased stiffness of vessel co-opted tumor cells, leading to improved AAT delivery. By using humanized patient-derived organoid xenografts with inhibited Wnt signaling, I will monitor tumor growth, its phenotype, and the response to AAT in vivo. Furthermore, I aim to pinpoint diagnostic markers for vessel co-option tumors using blood tests and computed tomography (CT) scans. Utilizing artificial intelligence tools, I plan to analyze CT scans of liver patients to better predict metastatic tumor subtypes and treatment responses in the future.
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.
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences physical sciences optics microscopy
- medical and health sciences clinical medicine oncology
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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.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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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) HORIZON-MSCA-2023-PF-01
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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.
8000 Aarhus C
Denmark
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.