Project description
KRAS cancer resistance and precision therapies
KRAS-mutant pancreatic and lung cancers are highly aggressive and currently lack effective targeted treatments. Supported by the Marie Skłodowska-Curie Actions programme, the KRATOS project aims to develop new treatment strategies for KRAS-mutant pancreatic and lung cancers, which currently rely mainly on limited chemotherapy options. It will use a systems-level approach combining experimental biology, phosphoproteomics and protein interaction mapping to understand how cancer signalling networks adapt to drug treatment and drive resistance. AI-guided computational modelling will then be used to identify drug targets and drug combinations. Overall, the project seeks to generate mechanistically informed therapies that can improve outcomes in some of the most lethal cancer types.
Objective
KRAS-mutant pancreatic and lung cancers are among the deadliest malignancies, with most patients lacking effective targeted therapies. The most common KRAS mutations, G12D and G12V, drive aggressive disease yet remain untreatable, leaving chemotherapy as the main option despite limited survival benefits and frequent resistance. Overcoming this challenge requires a systems-level strategy that goes beyond single-target approaches.
This project combines experimental biology, computational modelling, and AI-guided drug discovery to uncover and validate new therapeutic strategies. Using phosphoproteomics under drug perturbations, we will reconstruct dynamic signalling networks in a panel of patient-relevant KRAS-mutant cell lines to reveal how oncogenic pathways adapt under treatment with both targeted RAS inhibitors and standard chemotherapies. High-resolution mass spectrometry will then map the context-specific protein interactions of key oncogenic drivers such as KRAS, TP53, and AKT, providing complementary insight into mechanisms of resistance.
These multi-layered datasets will be integrated into Rezo Therapeutics’ “Sequence to Systems to Drugs” (SSD) platform, an AI-based pipeline that predicts and prioritises novel drug targets and rational combinations. The most promising candidates will subsequently be tested in advanced 3D patient-derived organoids and spheroid models, ensuring translational relevance.
By delivering mechanistically grounded drug combinations and a comprehensive resource on KRAS signalling and resistance, this fellowship will pave the way for precision-guided therapies in high-mortality cancers. It will also equip the researcher with cutting-edge expertise in systems biology, AI-driven discovery, and translational cancer models, while providing the leadership and transferable skills needed to establish an independent career that strengthens Europe’s capacity to tackle major challenges in oncology.
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.
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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)
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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-TMA-MSCA-PF-GF - HORIZON TMA MSCA Postdoctoral Fellowships - Global 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.
4 Dublin
Ireland
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.