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Innovative therapeutic tools to ameliorate chemotherapy-induced cardiotoxicity

Descrizione del progetto

Un nuovo farmaco per ridurre gli effetti collaterali della chemioterapia

La cardiotossicità indotta dalla chemioterapia è un problema importante associato ai trattamenti antitumorali, che causa gravi effetti collaterali come aritmia e insufficienza cardiaca. L’approccio attuale, che consiste nel ridurre le dosi per un periodo più lungo per mitigare questi effetti, ha un impatto negativo sulla qualità della vita. Esistono prove che implicano la via di segnalazione p38 nella cardiotossicità ma, nonostante lo sviluppo di molti inibitori, i risultati degli studi clinici sono stati finora deludenti. Il progetto p38_InTh, Finanziato dal Consiglio europeo della ricerca, intende migliorare la potenza di una nuova classe di inibitori della p38 e convalidarne il possibile uso terapeutico per migliorare la cardiotossicità indotta dai farmaci chemioterapici. Il progetto offre la speranza di un nuovo farmaco che potrebbe superare gli effetti collaterali della chemioterapia.

Obiettivo

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.

Meccanismo di finanziamento

ERC-POC - Proof of Concept Grant

Istituzione ospitante

FUNDACIO INSTITUT DE RECERCA BIOMEDICA (IRB BARCELONA)
Contribution nette de l'UE
€ 149 937,00
Indirizzo
CARRER BALDIRI REIXAC 10-12 PARC SCIENTIFIC DE BARCELONA
08028 Barcelona
Spagna

Mostra sulla mappa

Regione
Este Cataluña Barcelona
Tipo di attività
Research Organisations
Collegamenti
Costo totale
€ 149 937,50

Beneficiari (1)