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Targeting stromal cells to modify tumor mechanical microenvironment and optimize drug delivery

Objective

Current chemotherapeutic agents are potent enough to kill cancer cells. Nonetheless, failure of standard chemotherapies for many cancer types (e.g. pancreatic and breast cancers) is primarily attributed to these agents never reaching cancer cells in amounts sufficient for complete cure. In solid tumours, blood vessels are often compressed, drastically reducing perfusion, thus resulting in insufficient drug delivery. Vessel compression is a consequence of mechanical stresses accumulated within the tumour during progression. Alleviation of these stresses has the potential to reopen compressed vessels and improve tumour perfusion. Here, the applicant proposes to test the hypothesis that judicious depletion of stromal cells, namely the cancer-associated fibroblasts (CAFs), has the potential to alleviate stress levels in highly desmoplastic and hypoperfused tumours and, thus, enhance chemotherapy. To explore this hypothesis, a combination of cutting-edge computational and experimental techniques will be employed. Specifically, a structure-based biomechanical model will be developed to analyse the contribution of CAFs to the generation and transmission of forces within a tumour. Subsequently, in vivo studies will be performed in mice to validate model predictions and identify the degree of CAF depletion that optimizes the efficacy of treatment. Successful completion of the proposed research will reveal the role of CAFs on the biomechanical behaviour of tumours and contribute to developing a therapeutic strategy for treatment of hypovascular tumours. Therefore, the proposal negotiates a subject of considerable importance for European society and beyond. Furthermore, the proposed research and training will establish a bidirectional transfer of skills where the applicant’s expertise in cell mechanics will be complemented by the Host’s in cancer biophysics, thus enhancing the applicant’s scientific potential and professional maturity, and promoting European research.

Fields of science (EuroSciVoc)

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Programme(s)

Multi-annual funding programmes that define the EU’s priorities for research and innovation.

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.

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.

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.

(opens in new window) H2020-MSCA-IF-2014

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Coordinator

UNIVERSITY OF CYPRUS
Net EU contribution

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.

€ 151 648,80
Address
AVENUE PANEPISTIMIOU 2109 AGLANTZI
1678 Nicosia
Cyprus

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Region
Κύπρος Κύπρος Κύπρος
Activity type
Higher or Secondary Education Establishments
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Total cost

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.

€ 151 648,80
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