title: Improving the preclinical models for the study of chemotherapy-induced cardiotoxicity: a Position Paper of the Italian Working Group on Drug Cardiotoxicity and Cardioprotection.
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.
authors.affiliation: Center of Excellence on Aging, Institute of Cardiology, "G. d'Annunzio" University - Chieti, Chieti, Italy, rmadonna@unich.it.
authors.forename: Rosalinda
authors.initials: R
authors.lastname: Madonna
authors.forename: Christian
authors.initials: C
authors.lastname: Cadeddu
authors.forename: Martino
authors.initials: M
authors.lastname: Deidda
authors.forename: Donato
authors.initials: D
authors.lastname: Mele
authors.forename: Ines
authors.initials: I
authors.lastname: Monte
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Novo
authors.forename: Pasquale
authors.initials: P
authors.lastname: Pagliaro
authors.forename: Alessia
authors.initials: A
authors.lastname: Pepe
authors.forename: Paolo
authors.initials: P
authors.lastname: Spallarossa
authors.forename: Carlo Gabriele
authors.initials: CG
authors.lastname: Tocchetti
authors.forename: Concetta
authors.initials: C
authors.lastname: Zito
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Mercuro
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D066126:Cardiotoxicity / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D004195:Disease Models, Animal; D006801:Humans; D008929:Mitochondria, Heart / Q000187:drug effects / Q000502:physiology; D009369:Neoplasms / Q000188:drug therapy*; D020890:Neuregulin-1 / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D002316:Cardiotonic Agents; C094131:NRG1 protein, human; D020890:Neuregulin-1