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Improving the preclinical models for the study of chemotherapy-induced cardiotoxicity: a Position Paper of the Italian Working Group on Drug Cardiotoxicity and Cardioprotection

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Abstract

Although treatment for heart failure induced by cancer therapy has improved in recent years, the prevalence of cardiomyopathy due to antineoplastic therapy remains significant worldwide. In addition to traditional mediators of myocardial damage, such as reactive oxygen species, new pathways and target cells should be considered responsible for the impairment of cardiac function during anticancer treatment. Accordingly, there is a need to develop novel therapeutic strategies to protect the heart from pharmacologic injury, and improve clinical outcomes in cancer patients. The development of novel protective therapies requires testing putative therapeutic strategies in appropriate animal models of chemotherapy-induced cardiomyopathy. This Position Paper of the Working Group on Drug Cardiotoxicity and Cardioprotection of the Italian Society of Cardiology aims to: (1) define the distinctive etiopatogenetic features of cardiac toxicity induced by cancer therapy in humans, which include new aspects of mitochondrial function and oxidative stress, neuregulin-1 modulation through the ErbB receptor family, angiogenesis inhibition, and cardiac stem cell depletion and/or dysfunction; (2) review the new, more promising therapeutic strategies for cardioprotection, aimed to increase the survival of patients with severe antineoplastic-induced cardiotoxicity; (3) recommend the distinctive pathological features of cardiotoxicity induced by cancer therapy in humans that should be present in animal models used to identify or to test new cardioprotective therapies.

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Abbreviations

CHF:

Congestive heart failure

ROS:

Reactive oxygen species

NRG-1:

Neuregulin-1

Top2:

Topoisomerase II

PI3:

Phosphoinositide-3

AKT:

Protein kinase B

MEK/ERK:

Mitogen extracellular kinase

TK:

Tyrosine kinase

VEGFR:

Vascular endothelial growth factor receptor

PDGFR:

Platelet-derived growth factor receptor

CSCs:

Cardiac stem cells

CPCs:

Cardiac progenitor cells

ACE:

Angiotensin-converting enzyme

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Authors and Affiliations

  1. Center of Excellence on Aging, Institute of Cardiology, “G. d’Annunzio” University – Chieti, Chieti, Italy

    Rosalinda Madonna

  2. Texas Heart Institute, Houston, TX, USA

    Rosalinda Madonna

  3. Cardiology Division, Department of Internal Medicine, University of Texas Medical School, Houston, TX, USA

    Rosalinda Madonna

  4. Department of Medical Sciences “Mario Aresu”, University of Cagliari, Cagliari, Italy

    Christian Cadeddu, Martino Deidda & Giuseppe Mercuro

  5. Cardiology Unit, University Hospital of Ferrara, Ferrara, Italy

    Donato Mele

  6. Department of General Surgery and Medical-Surgery Specialties, University of Catania, Catania, Italy

    Ines Monte

  7. Chair and Division of Cardiology, University of Palermo, Palermo, Italy

    Giuseppina Novo

  8. Department of Clinical and Biological Sciences, University of Turin, Orbassano, Italy

    Pasquale Pagliaro

  9. U.O.C. Magnetic Resonance Imaging, Fondazione G. Monasterio C.N.R., Pisa, Italy

    Alessia Pepe

  10. Clinic of Cardiovascular Diseases, IRCCS San Martino IST, Genoa, Italy

    Paolo Spallarossa

  11. Division of Internal Medicine, Department of Translational Medical Sciences, Federico II University, Naples, Italy

    Carlo Gabriele Tocchetti

  12. U.O.C. Cardiology Intensive Unit, A.O.U. Policlinico “G. Martino”, University of Messina, Messina, Italy

    Concetta Zito

Authors
  1. Rosalinda Madonna
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  2. Christian Cadeddu
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  3. Martino Deidda
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  4. Donato Mele
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  5. Ines Monte
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  6. Giuseppina Novo
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  7. Pasquale Pagliaro
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  8. Alessia Pepe
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  9. Paolo Spallarossa
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  10. Carlo Gabriele Tocchetti
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  11. Concetta Zito
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  12. Giuseppe Mercuro
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Corresponding author

Correspondence to Rosalinda Madonna.

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Madonna, R., Cadeddu, C., Deidda, M. et al. Improving the preclinical models for the study of chemotherapy-induced cardiotoxicity: a Position Paper of the Italian Working Group on Drug Cardiotoxicity and Cardioprotection. Heart Fail Rev 20, 621–631 (2015). https://doi.org/10.1007/s10741-015-9497-4

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