Objective
Malignant rhabdoid tumours (MRTs) are among the most aggressive paediatric cancers, with overall survival rates below 30%. The genetic hallmark of MRTs is the biallelic inactivation of SMARCB1 (or, rarely, SMARCA4). This single-driver, loss-of-function alteration disrupts epigenetic regulation, leading to uncontrolled proliferation and impaired differentiation. Unlike many cancers with complex mutational landscapes, MRTs are largely epigenetically driven, which raises the possibility that restoration of SMARCB1 function could reverse malignant phenotypes. Current treatment relies on highly toxic chemotherapy and radiotherapy regimens, which provide limited benefit and cause severe long-term side effects. No targeted therapies exist, underscoring an urgent unmet clinical need.
BEAT-MRT builds on ERC-funded discoveries demonstrating that reintroduction of SMARCB1 halts proliferation and induces differentiation in MRT models, establishing a therapeutic opportunity. We will test whether CRISPR-mediated base editing can be used to correct SMARCB1 mutations in vivo, delivered through engineered virus-like particles or adeno-associated virus vectors. Using luciferase-expressing patient-derived xenograft models, tumour progression will be monitored in real time, and efficacy will be measured as reduced tumour growth and prolonged survival. Molecular analyses will validate SMARCB1 repair and confirm safety.
The main project outcome will be the demonstration that targeted genomic correction of SMARCB1 can control MRT progression in vivo. If successful, this would establish a first-in-class therapeutic approach for a devastating childhood cancer and provide a proof of principle for treating monogenic, epigenetically driven malignancies through functional gene restoration. This PoC will also assess IP, market potential, and business strategy, laying the groundwork for translational development and follow-up funding opportunities.
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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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)
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-ERC-POC - HORIZON ERC Proof of Concept 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-2026-POC
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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.
3584CS Utrecht
Netherlands
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.