Objective
Pancreatic ductal adenocarcinoma (PDAC) is a life-threatening disease with few treatment options. Recently, the chemical space for targeted therapeutics was significantly increased by the development of compounds that induce protein degradation (PROTACs), but so far, they are unavailable for PDAC. The main motivation of PROTAC-PDAC is to develop novel targeted therapies for PDAC. The project is based on our accomplishments in three crucial areas. First, my group identified – as target candidates – a series of transcription factors that are absolutely required for PDAC growth in vivo. Second, we developed dozens of potent, specific PROTACs, thereby gaining deep insight into the underlying design principles and synthesis procedures. Third, we established genetic models in mice for simulating PROTAC function and discovering ideal target–E3 ligase pairs.
In PROTAC-PDAC, we will develop compounds that degrade key oncogenic transcription factors and inhibit pancreatic tumor growth with minimal toxicity in healthy tissues. We will start by implementing the Auxin degron system in a murine PDAC model, to induce degradation of the target candidates and select four priority targets with the highest therapeutic index (Aim I). Then, we will assess their oncogenic functions by analyzing molecular, cellular and organismic consequences of acute depletion in mice (Aim II). In parallel, we will develop pharmaceutical PROTACs to induce target degradation and analyze their efficacy in PDAC models (Aim III). Finally, with the aim of developing less toxic PDAC therapy, we will identify pancreatic E3 ligases for the design of the first tissue-specific PROTACs that induce target degradation primarily in pancreatic tumor cells (Aim IV).
While the main goal of PROTAC-PDAC is to develop new PROTAC-based therapeutic strategies, we will also establish groundbreaking methods and models leading to fundamental discoveries in PDAC biology.
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 prostate cancer
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences medical biotechnology cells technologies
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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.1.1 - European Research Council (ERC)
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-ERC - HORIZON ERC 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-COG
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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.
24118 Kiel
Germany
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.