Project description
Targeting tumour stiffness
Tissues naturally exhibit stiffness, which allows them to sense and respond to mechanical forces and resist deformation. This stiffness depends on the tissue’s composition and extracellular matrix. In many solid tumours, increased rigidity drives cancer progression. The ERC-funded INTROPY project focuses on a protein that unfolds specifically in stiff tissues, representing a novel target for therapy. The project aims to inhibit this protein to block stiffness-driven cancer progression. The research team will test promising compounds in cellular models, optimise their properties with medicinal chemistry, and provide proof-of-concept evidence for their potential as first-in-class therapeutics.
Objective
Increased tissue stiffness is a hallmark of many solid tumours, driving tumour progression. This occurs through mechanotransduction, the process by which cells sense and respond to mechanical signals. Our lab has identified a key interaction between two proteins, essential for mechanotransduction. This interaction is triggered by force-induced unfolding of a target protein, which occurs only in stiff tissues. Hence, we propose a novel therapeutic approach that targets mechanotransduction by inhibiting the stiffness-induced unfolding of the target protein. This innovative approach has the potential to transform cancer therapy and provide new insights into the role of mechanical signals in disease progression. We developed a thermal shift assay to identify molecules that stabilize the target and inhibit its unfolding. High throughput Screening (HTS) of ~5,000 molecules resulted in 4 hits with confirmed specific binding by NMR analysis. Two additional hits were identified each through structure-based virtual screening and a peptide-based approach, with confirmed binding through NMR analysis. In this project, we aim to validate these 6 hits, and to provide proof-of-concept evidence of their potential for cancer therapy. First, we will validate hits in vitro and in cellular assays. Second, we will optimize them with medicinal chemists to obtain lead molecules. Third, we will evaluate resulting lead molecules in an in vivo mouse breast cancer model. By the end of the project, we expect our data to be sufficient to attract private investment and establish a spin-off company to pursue drug development into clinical phases. This will lead to a first-inclass mechanoinhibitor drug, with potential applications in cancer (with a focus on breast and pancreatic cancer) and other conditions characterized by mechanical stress, such as fibrosis.
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
- medical and health sciences clinical medicine oncology
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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)
MAIN PROGRAMME
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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.
HORIZON-ERC-POC - HORIZON ERC Proof of Concept Grants
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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) ERC-2024-POC
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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.
08028 Barcelona
Spain
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.