Project description
Uncovering chemoresistance in cholangiocarcinoma for personalised treatment
Cholangiocarcinoma (CCA) is an increasingly common form of liver cancer. Unfortunately, it is often diagnosed at an advanced stage. It also responds poorly to existing treatments. Supported by the Marie Skłodowska-Curie Actions programme, the RESIST-CCA project uses advanced single-cell analysis techniques and a patient-specific CCA-on-a-chip model to identify the tumour cell subpopulations responsible for treatment resistance. Then it will test targets for intervention. The project’s goal is to develop personalised treatment strategies that can overcome chemoresistance and improve outcomes for patients.
Objective
Cholangiocarcinoma (CCA) is a highly heterogeneous and aggressive group of malignant tumours arising along the biliary tree. Its incidence (~5:100,000) is rising worldwide, and it already represents the second most common primary liver cancer (10–15%). Alarmingly, CCA-related mortality has increased by 37% in Europe over the past two decades, establishing CCA as a major health, social, and economic burden. The delayed diagnosis of CCA, combined with its pronounced chemoresistance, results in an extremely poor prognosis, with 5-year survival rates below 10%.
The RESIST-CCA project aims to unravel the molecular and cellular footprint of specific cholangiocyte subpopulations that drive chemoresistance in CCA. Using cutting-edge single-cell and spatial transcriptomics within a patient-specific CCA-on-a-chip model, the project will identify resistant subclones, characterize their molecular signatures, and define their interactions with the tumour microenvironment that enable therapeutic escape. This work will uncover key pathways associated with chemoresistance. Identified mechanisms will be functionally validated through gene editing (CRISPR/Cas9 or RNAi) and pharmacological inhibition, using both the personalized CCA-on-chip microfluidic platform and in vivo patient-derived xenografts (PDX).
Overall, RESIST-CCA will generate a high-resolution atlas of chemoresistance in CCA, with a particular focus on the functional impact of intratumoural cholangiocyte heterogeneity. These insights will guide the development of tailored, resistance-guided therapeutic strategies aimed at re-sensitizing specific cholangiocyte subsets. By addressing the underexplored role of cholangiocyte heterogeneity, RESIST-CCA will provide a transformative framework for understanding and overcoming chemoresistance in CCA, with broad implications for other heterogeneous and treatment-refractory cancers.
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 liver cancer
- social sciences sociology demography mortality
- medical and health sciences medical biotechnology genetic engineering gene therapy
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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)
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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
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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
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(opens in new window) HORIZON-MSCA-2025-PF
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20100 Rozzano (Mi)
Italy
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