Project description
Targeting squamous cell carcinoma microenvironment as a treatment strategy
Cancer stem cells (CSC) initiate and sustain the resistance of skin squamous cell carcinomas (SCC) to treatment. CSC proliferation is governed by genetic mutations and by interactions between CSC and the microenvironment. Targeting the microenvironment represents a promising approach in SCC treatment. Using mouse models of SCC, previous work from the project team showed a direct interaction between skin CSC and tumour-associated macrophages (TAM) via Wnt signalling. Wnt regulates the expression of three CSC receptors, CD99, MFGE8 and Nectin-2, which govern the CSC–TAM crosstalk. The EU-funded CApaCITy project will expand these results into translational research, exploring the potential of CD99, MFGE8 and Nectin-2 as therapeutic targets for human SCC.
Objective
Cancer stem cells (CSC) initiate, sustain the prevalence, and resistance to therapy of skin squamous cell carcinomas (SCC). It is well acknowledged that CSC self-renewal and clonal growth is governed by genetic mutations, but also by complex interactions between CSC and the microenvironment. Genetic therapy is difficult to achieve in clinical settings, therefore, targeting cells of the supportive tumor microenvironment is a promising advance to eradicate SCC.
Using mouse models of SCC, our previous basic research results uncovered the existence of a direct crosstalk between skin CSC and tumor-associated macrophages (TAM) via Wnt signaling. Interestingly, we observed that Wnt regulated the expression of three CSC receptors, CD99, MFGE8 and Nectin-2, and governed the CSC-TAM crosstalk. Here, I propose to expand this basic research into a translational perspective, to explore the potential of CD99, MFGE8 and Nectin-2 as therapeutic targets for human SCC. There is a major interest in this arena, since the major caveat of targeting Wnt signaling in cancer is the lack of specificity to target CSC, without affecting somatic cells. Moreover, most clinical trials have not been fully efficient to dampen the Wnt response in tumors. Using a comprehensive and integrated approach based on human SCC, cell biology, omics and medical chemistry, along with powerful patient derived xerographs (PDX), my results must likely unearth a role for these immunoreceptors in governing the CSC-TAM crosstalk, and their potential as drug targets for human SSC. This interdisciplinary project will be conducted at the University of Copenhagen (UCPH) in Dr. Perez-Moreno, Dr. Merete Haedersdal, and Dr. Strømgaard groups. Through the CApaCITy project, I will embark in a leading research area with several possibilities to grow into an independent international researcher.
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 skin cancer squamous cell carcinoma
- natural sciences biological sciences cell biology
- medical and health sciences medical biotechnology cells technologies stem cells
- natural sciences biological sciences genetics mutation
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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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H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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Topic(s)
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.
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.
MSCA-IF-EF-ST - Standard EF
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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) H2020-MSCA-IF-2018
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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.
1165 KOBENHAVN
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.