Models of Heart Failure Based on the Cardiotoxicity of Anticancer Drugs

Valentina Mercurio, Flora Pirozzi, Edoardo Lazzarini, Giancarlo Marone, Paola Rizzo, Giulio Agnetti, Carlo G. Tocchetti, Alessandra Ghigo, Pietro Ameri

Research output: Contribution to journalReview articlepeer-review

35 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)449-458
Number of pages10
JournalJournal of cardiac failure
Issue number6
StatePublished - Jun 1 2016


  • Heart failure
  • anthracyclines
  • antineoplastic drugs-induced cardiotoxicity
  • receptor tyrosine kinase

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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