Description du projet
Cibler le dysfonctionnement mitochondrial dans la cardiotoxicité suite à un traitement contre le cancer
Le traitement contre le cancer peut mener à une toxicité cardiaque et éventuellement à une insuffisance cardiaque dans près de 30 % des cas. Toutefois, les thérapies actuelles contre la cardiotoxicité induite par les traitements anti-cancéreux (CTiCT) sont sous-optimales et initiées trop tard. Le projet MATRIX, financé par l’UE, vérifie l’hypothèse selon laquelle la CTiCT est associée à une dynamique mitochondriale altérée dans les cardiomyocytes et propose d’inverser la reprogrammation métabolique en guise de traitement. Les chercheurs ont développé une technique d’imagerie basée sur un algorithme pour la détection précoce des dommages myocardiques et le lancement rapide d’une thérapie. En outre, ils envisagent de transplanter des mitochondries pour traiter le dysfonctionnement mitochondrial dans la CTiCT en phase terminale.
Objectif
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.
Champ scientifique
Programme(s)
Régime de financement
ERC-COG - Consolidator GrantInstitution d’accueil
28029 Madrid
Espagne