Models of Heart Failure Based on the Cardiotoxicity of Anticancer Drugs.
Heart failure (HF) is a complication of oncological treatments that may have dramatic clinical impact. It may acutely worsen a patient's condition or it may present with delayed onset, even years after treatment, when cancer has been cured or is in stable remission. Several studies have addressed the mechanisms of cancer therapy-related HF and some have led to the definition of disease models that hold valid for other and more common types of HF. Here, we review these models of HF based on the cardiotoxicity of antineoplastic drugs and classify them in cardiomyocyte-intrinsic, paracrine, or potentially secondary to effects on cardiac progenitor cells. The first group includes HF resulting from the combination of oxidative stress, mitochondrial dysfunction, and activation of the DNA damage response, which is typically caused by anthracyclines, and HF resulting from deranged myocardial energetics, such as that triggered by anthracyclines and sunitinib. Blockade of the neuregulin-1/ErbB4/ErbB2, vascular endothelial growth factor/vascular endothelial growth factor receptor and platelet-derived growth factor /platelet-derived growth factor receptor pathways by trastuzumab, sorafenib and sunitinib is proposed as paradigm of cancer therapy-related HF associated with alterations of myocardial paracrine pathways. Finally, anthracyclines and trastuzumab are also presented as examples of antitumor agents that induce HF by affecting the cardiac progenitor cell population.
Division of Internal Medicine, Department of Translational Medical Sciences, Federico II University, Naples, Italy.
Valentina
V
Mercurio
Division of Internal Medicine, Department of Translational Medical Sciences, Federico II University, Naples, Italy.
Flora
F
Pirozzi
Laboratory of Cardiovascular Biology, Department of Internal Medicine, University of Genova, Genova, Italy.
Edoardo
E
Lazzarini
Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy.
Giancarlo
G
Marone
Department of Morphology, Surgery and Experimental Medicine and Laboratory for Technologies of Advanced Therapies, University of Ferrara, Ferrara, Italy.
Paola
P
Rizzo
Johns Hopkins University, Cardiology, Baltimore, Maryland; Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
Giulio
G
Agnetti
Division of Internal Medicine, Department of Translational Medical Sciences, Federico II University, Naples, Italy. Electronic address: carlogabriele.tocchetti@unina.it.
Carlo G
CG
Tocchetti
Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy.
Alessandra
A
Ghigo
Laboratory of Cardiovascular Biology, Department of Internal Medicine, University of Genova, Genova, Italy.
Pietro
P
Ameri
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D066126:Cardiotoxicity; D006333:Heart Failure / Q000139:chemically induced*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*
D000970:Antineoplastic Agents
Heart failure; anthracyclines; antineoplastic drugs-induced cardiotoxicity; receptor tyrosine kinase