Objective
SAFE-LIVER aims to establish proof-of-concept for a first-in-class metabolic hepatoprotectant that enables safe delivery of cancer therapies in patients with compromised liver function. Liver toxicity is a major barrier to curative cancer therapy. Radiotherapy and chemotherapy frequently cause hepatic injury that limits treatment intensity or excludes patients entirely. This problem is particularly severe in patients with pre-existing liver disease such as non-alcoholic fatty liver disease (NAFLD), which affects ~25–35% of adults globally. As a result, many patients with liver tumours or liver metastases cannot safely receive potentially curative therapy. Currently, no effective pharmacological hepatoprotectant exists.
Building on discoveries from my ERC Advanced Grant TETHER, we identified the mitochondrial enzyme ECHDC2 as a previously unrecognized regulator of oxidative stress and radiotherapy response. Genetic loss of ECHDC2 increases malonyl-CoA, suppresses mitochondrial fatty-acid oxidation, and activates an endogenous NRF2-mediated antioxidant program. Importantly, Echdc2 knockout mice are viable and display significantly reduced DNA damage in the liver after irradiation, demonstrating intrinsic hepatoprotection.
SAFE-LIVER will determine whether transient inhibition of ECHDC2 can protect the liver during cancer therapy without compromising tumor control. We will validate genetic protection in Echdc2-deficient mice, demonstrate pharmacological feasibility using liver-targeted GalNAc-siRNA and pathway modulators, and define the therapeutic window in tumor-bearing models.
If successful, SAFE-LIVER will enable safer radiotherapy and other hepatotoxic cancer treatments in patients with vulnerable livers, expand access to curative therapies, and create a first-in-class platform for metabolic organ protection. The project will also generate the translational data required to advance the technology towards industrial partnership and clinical development.
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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.
3012 Bern
Switzerland
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.