Descripción del proyecto
Concentración en la disfunción de las mitocondrias en la cardiotoxicidad provocada por tratamientos oncológicos
Los tratamientos oncológicos pueden provocar toxicidad cardíaca y, con el tiempo, insuficiencia cardíaca en casi el 30 % de los casos. Con todo, las terapias actuales para la cardiotoxicidad inducida por tratamientos oncológicos (CTiCT, por sus siglas en inglés) son subóptimas y se inician demasiado tarde. El proyecto financiado con fondos europeos MATRIX trabaja con la hipótesis de que la CTiCT está relacionada con la alteración de la dinámica mitocondrial en los cardiomiocitos y propone revertir la reprogramación metabólica como tratamiento. Los investigadores han desarrollado una técnica de imagenología basada en algoritmos para la detección temprana de daños mitocondriales y el rápido inicio de la terapia. Además, prevén trasplantar mitocondrias para corregir la disfunción en una etapa temprana de la CTiCT.
Objetivo
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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ERC-COG - Consolidator GrantInstitución de acogida
28029 Madrid
España