Project description
Mapping treatment resistance in paediatric glioma
Paediatric gliomas represent the most common malignant brain tumours in children, and relapse after targeted therapy remains a major clinical challenge. In a subset of these tumours, the gene BRAF is identified as a key oncogenic driver. This gene encodes a protein kinase that regulates cell growth through the MAPK signalling pathway. Paediatric gliomas carrying the BRAF V600E mutation exhibit constant activation of the BRAF protein. While dual BRAF/MEK inhibition improves clinical outcomes, resistance often emerges through poorly understood non-genetic mechanisms. With the support of the Marie Skłodowska-Curie Actions programme, the PEDGLIORES project will follow a multidisciplinary approach to map treatment responses and reveal how resistant cells arise, with potential implications for future precision oncology strategies.
Objective
Paediatric gliomas are the most common malignant brain tumours in children, and despite advances in molecular classification and targeted therapies, resistance to treatment remains a major clinical challenge. In BRAFV600E-mutant gliomas, dual BRAF/MEK inhibition has improved outcomes, but more than half of patients relapse within two years. Increasing evidence suggests that resistance is often driven not by genetic mutations, but by reversible, non-genetic mechanisms such as epigenetic reprogramming. However, these processes remain poorly understood in paediatric glioma.
This project addresses this gap by integrating single-cell transcriptomic and epigenomic data with proteomic data in a multimodal, time-resolved framework. Patient-derived explants and xenografts treated with targeted therapy are being profiled at multiple time points using cutting-edge assays that jointly capture gene expression and histone modifications, alongside direct measurements of kinase activity. We will develop and implement computational tools for multimodal data integration, including optimal transport models to track population dynamics over time and causal network inference to connect kinase signalling, transcription factor activity, and downstream gene regulation. This design will allow us to capture the mechanisms by which persister and resistant cells emerge and survive with unprecedented resolution.
The project builds on an existing collaboration between groups at Institut Curie (Paris), the University Children’s Hospital Zurich, and the University of California, San Francisco. By integrating data across models, we aim to create the first single-cell multi-omic atlas of paediatric glioma under treatment. The expected outcome is the identification of actionable kinases and pathways driving relapse, informing preclinical testing and potentially guiding early-phase clinical trials. The approach can be extended to other BRAFV600E tumours or cancers with similar resistance mechanisms.
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.
This project's classification has been human-validated.
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.
This project's classification has been human-validated.
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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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
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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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75231 Paris
France
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