Objective
With more than 1.9 million new cases and 935,000 related deaths in 2020, colorectal cancer (CRC) is the third most common cancer in men and the second in women. While surgery is the main treatment option for lower grade CRC, patients with unresectable lesions are treated with chemotherapy. Related therapies are associated with severe drawbacks, such as systemic toxicity, low response rate, and unpredictable resistance. Molecular targeted therapies have emerged as a promising strategy to specifically target cancer cells. For CRC, the inhibition of the Wnt signalling pathway has moved into the focus of novel therapeutic approaches as it is hyperactivated in 80% of all cases. Within the pathway, the protein beta-catenin is considered a particularly attractive target. However, classic small molecule targeting strategies have failed to provide any approved drugs that inhibit beta-catenin so far.
We have identified a family of peptidomimetic agents that bind beta-catenin and inhibit its interaction with the TCF/LEF transcription factors. For the first time, it was possible to obtain a crystal structure of a synthetic molecule bound to a therapeutically very attractive site on beta-catenin. In addition, we have confirmed cellular activity of these inhibitors verifying selective inhibition of the Wnt signalling pathway. These findings provide the ideal starting point for the development of novel therapeutics for Wnt-dependent cancers, in particular for CRC. These first-in-class inhibitors will provide the basis for the development of therapeutics that selectively inhibit oncogenic Wnt signalling thereby affecting the viability of corresponding cancer cells. This can enable targeted therapies for Wnt-dependent forms of CRC.
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 cell biology cell signaling
- medical and health sciences clinical medicine surgery
- 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-2022-POC1
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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.
1081 HV Amsterdam
Netherlands
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.