Project description
A new drug to potentially reduce chemotherapy side effects
Chemotherapy-induced cardiotoxicity is a major issue associated with cancer treatments, causing serious side effects such as arrhythmia and heart failure. The current approach of reducing doses for a longer period to mitigate these effects negatively impacts quality of life. There is evidence implicating the p38 signalling pathway in cardiotoxicity, but despite the development of many inhibitors, the results in clinical trials have been disappointing so far. Funded by the European Research Council, the p38_InTh project aims to improve the potency of a new class of p38 inhibitors and validate their potential therapeutic use to ameliorate the cardiotoxicity induced by chemotherapy drugs. The project will offer hope for a new drug that could overcome the side effects of chemotherapy.
Objective
p38_InTh aims at improving the potency of a new class of highly specific p38 pathway inhibitors and validate their potential therapeutic use to ameliorate chemotherapy-induced cardiotoxicity without affecting the cancer cell toxicity of the chemotherapeutic. Chemotherapeutics used for cancer treatments have serious side effects, both the most broad-spectrum ones (such as anthracyclines) and the directed ones (such as trastuzumab). In particular, the cardiotoxicity is a major issue associated to chemotherapy. Cardiooncology research has recently emerged to tackle this serious unmet medical need. The cardiotoxicity induced by chemotherapeutics includes from arrhythmia to heart failure. To mitigate it, cardiooncologists usually adjust the treatment with reduced doses for a longer period, but this makes the anticancer treatments less efficient and consequently reduces the quality of life of the patients. There is evidence that cardiomyocyte death induced by anthracyclines involves activation of a specific p38 pathway, suggesting that inhibition of this pathway may reduce the cardiotoxicity associated with chemotherapeutics. Over the last two decades, many p38 pathway inhibitors have been developed by industry. However, these are mostly ATP competitors and have shown disappointing results in clinical trials. In contrast, we have recently identified novel compounds that inhibit only one of the target isoforms and through a novel MoA, selectively antagonizing the activation of this isoform by one of its protein partners. We propose to improve the potency of these hits and validate their potential therapeutic use to ameliorate chemotherapy-induced cardiotoxicity without affecting the cancer cell toxicity. Importantly, our new drug would inhibit only a subset of the p38 pathway regulated functions, which is expected to result in increased specificity, thereby overcoming the undesired side-effects found in clinical trials for the classical ATP competitive p38 pathway inhibitors.
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 cardiology cardiovascular diseases cardiac arrhythmia
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences clinical medicine oncology
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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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H2020-EU.1.1. - EXCELLENT SCIENCE - 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.
ERC-POC - Proof of Concept Grant
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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-2018-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.
08028 BARCELONA
Spain
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.