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Novel mitochondria-targeted therapies for cancer treatment-induced cardiotoxicity

Novel mitochondria-targeted therapies for cancer treatment-induced cardiotoxicity

Objective

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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Host institution

CENTRO NACIONAL DE INVESTIGACIONESCARDIOVASCULARES CARLOS III (F.S.P.)

Address

Calle Melchor Fernandez Almagro 3
28029 Madrid

Spain

Activity type

Research Organisations

EU Contribution

€ 1 473 437,50

Beneficiaries (2)

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CENTRO NACIONAL DE INVESTIGACIONESCARDIOVASCULARES CARLOS III (F.S.P.)

Spain

EU Contribution

€ 1 473 437,50

INSTITUTO INVESTIGACION SANITARIA FUNDACION JIMENEZ DIAZ

Spain

EU Contribution

€ 525 937,50

Project information

Grant agreement ID: 819775

Status

Grant agreement signed

  • Start date

    1 September 2019

  • End date

    31 August 2024

Funded under:

H2020-EU.1.1.

  • Overall budget:

    € 1 999 375

  • EU contribution

    € 1 999 375

Hosted by:

CENTRO NACIONAL DE INVESTIGACIONESCARDIOVASCULARES CARLOS III (F.S.P.)

Spain