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Biochemistry Research International
Volume 2012 (2012), Article ID 951539, 12 pages
Review Article

Mitochondria Death/Survival Signaling Pathways in Cardiotoxicity Induced by Anthracyclines and Anticancer-Targeted Therapies

Department of Physiology (EA4484), Faculty of Medicine, University of Lille 1, Place de Verdun, 59045 Lille, France

Received 16 November 2011; Revised 4 January 2012; Accepted 9 January 2012

Academic Editor: Catherine Brenner

Copyright © 2012 David Montaigne et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Anthracyclines remain the cornerstone of treatment in many malignancies but these agents have a cumulative dose relationship with cardiotoxicity. Development of cardiomyopathy and congestive heart failure induced by anthracyclines are typically dose-dependent, irreversible, and cumulative. Although past studies of cardiotoxicity have focused on anthracyclines, more recently interest has turned to anticancer drugs that target many proteins kinases, such as tyrosine kinases. An attractive model to explain the mechanism of this cardiotoxicity could be myocyte loss through cell death pathways. Inhibition of mitochondrial transition permeability is a valuable tool to prevent doxorubicin-induced cardiotoxicity. In response to anthracycline treatment, activation of several protein kinases, neuregulin/ErbB2 signaling, and transcriptional factors modify mitochondrial functions that determine cell death or survival through the modulation of mitochondrial membrane permeability. Cellular response to anthracyclines is also modulated by a myriad of transcriptional factors that influence cell fate. Several novel targeted chemotherapeutic agents have been associated with a small but worrying risk of left ventricular dysfunction. Agents such as trastuzumab and tyrosine kinase inhibitors can lead to cardiotoxicity that is fundamentally different from that caused by anthracyclines, whereas biological effects converge to the mitochondria as a critical target.