Projektbeschreibung
Mitochondrienstörungen bei Kardiotoxizität nach Krebsbehandlung im Visier
Eine Krebsbehandlung kann zu Kardiotoxizität und in nahezu 30 % der Fälle schließlich zu Herzversagen führen. Doch bestehende Therapien für die krebsinduzierte Kardiotoxizität (CTiCT) sind suboptimal und werden zu spät eingeleitet. Das EU-finanzierte Projekt MATRIX arbeitet unter der Hypothese, dass die CTiCT mit einer veränderten mitochondrialen Dynamik in Herzmuskelzellen verbunden ist, und schlägt als Behandlung eine metabolische Umprogrammierung vor. Forschende haben ein algorithmusgestütztes Bildgebungsverfahren zur Früherkennung von Myokardschäden und schnellen Therapieeinleitung entwickelt. Ferner beabsichtigen sie die Transplantation von Mitochondrien, um mitochondriale Störungen im Endstadium einer CTiCT anzugehen.
Ziel
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.
Wissenschaftliches Gebiet
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Finanzierungsplan
ERC-COG - Consolidator GrantGastgebende Einrichtung
28029 Madrid
Spanien