Objective
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers, with a five‑year survival rate below 5%, making it a significant global health challenge. Despite extensive research, gemcitabine remains the standard first‑line treatment, but its effectiveness is constrained by rapid resistance and poor patient stratification. The human equilibrative nucleoside transporter 1 (hENT1) plays a key role in gemcitabine uptake and serves as a promising biomarker for predicting treatment response. Recent ligand-bound crystal structures of hENT1 enable atomic‑level investigation of its dynamics and resistance‑linked mutations. The present project aims to uncover the molecular basis of gemcitabine transport and resistance using a unified approach that combines computational structural biology with AI-guided drug design. We will first identify and model hENT1 mutations associated with PDAC progression, then characterize gemcitabine binding to both wild‑type and mutant transporters via molecular docking complemented by extended molecular dynamics simulations. Finally, generative adversarial networks (GANs) will be employed to design gemcitabine analogs with enhanced efficacy against resistant variants. These efforts will elucidate hENT1‑mediated drug transport mechanisms, guide the rational development of next‑generation nucleoside analogs, and support biomarker‑driven therapeutic strategies in PDAC.
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 computer and information sciences artificial intelligence generative artificial intelligence
- natural sciences biological sciences genetics mutation
- natural sciences biological sciences molecular biology structural biology
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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.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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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) HORIZON-MSCA-2025-PF
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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.
S10 2TN SHEFFIELD
United Kingdom
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.