Descrizione del progetto
Intervenire sulla disfunzione mitocondriale nella cardiotossicità indotta da trattamenti contro il cancro
I trattamenti contro il cancro possono comportare la cardiotossicità e infine l’insufficienza cardiaca in quasi il 30 % dei casi. Tuttavia, le terapie esistenti per la cardiotossicità indotta da trattamenti contro il cancro non sono ottimali e vengono avviate in ritardo. Il progetto MATRIX, finanziato dall’UE, sta lavorando nell’ambito dell’ipotesi secondo la quale questa cardiotossicità sia correlata a dinamiche mitocondriali alterate nei cardiomiociti e propone di ricorrere alla riprogrammazione metabolica come trattamento. I ricercatori hanno sviluppato una tecnica per immagini basata su algoritmo per la diagnosi precoce di danni miocardiaci e per l’avvio tempestivo della terapia. Inoltre, essi prevedono di trapiantare i mitocondri per affrontare la disfunzione mitocondriale in tale cardiotossicità indotta allo stadio finale.
Obiettivo
Cardiac toxicity is one of the most frequent serious side effects of cancer therapy, affecting up to 30% of treated patients. Cancer treatment-induced cardiotoxicity (CTiCT) can result in severe heart failure. The trade-off between cancer and chronic heart failure is an immense personal burden with physical and psychological consequences. Current therapies for CTiCT are suboptimal, featuring poor early detection algorithms and nonspecific heart failure treatments. Based on our recently published results and additional preliminary data presented here, we propose that CTiCT is associated with altered mitochondrial dynamics, triggering a cardiomyocyte metabolic reprogramming. MATRIX represents a holistic approach to tackling mitochondrial dysfunction in CTiCT. Our hypothesis is that reverting metabolic reprogramming by shifting mitochondrial substrate utilization could represent a new paradigm in the treatment of early-stage CTiCT. By refining a novel imaging-based algorithm recently developed in our group, we will achieve very early detection of myocardial damage in patients treated with commonly prescribed cancer therapies, long before clinically used parameters become abnormal. Such early detection, not available currently, is crucial for implementation of early therapies. We also hypothesize that in end-stage CTiCT, mitochondrial dysfunction has passed a no-return point, and the failing heart will only be rescued by a strategy to replenish the myocardium with fresh healthy mitochondria. This will be achieved with a radical new therapeutic option: in-vivo mitochondrial transplantation. The MATRIX project has broad translational potential, including a new therapeutic approach to a clinically relevant condition, the development of technology for early diagnosis, and advances in knowledge of basic disease mechanisms.
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Meccanismo di finanziamento
ERC-COG - Consolidator GrantIstituzione ospitante
28029 Madrid
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