Anthracyclines/trastuzumab: new aspects of cardiotoxicity and molecular mechanisms

•Anthracyclines and trastuzumab are effective chemotherapies that can cause cardiotoxicity.•Cardiotoxicity is due to a combination of ‘on-target’ and ‘off-target’ effects.•Neuregulin-1 in the microvascular endothelium is involved in cardiotoxicity.•ErbB2 could be a potential target for anticancer th...

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Bibliographic Details
Published in:Trends in pharmacological sciences (Regular ed.) Vol. 36; no. 6; pp. 326 - 348
Main Authors: Rochette, Luc, Guenancia, Charles, Gudjoncik, Aurélie, Hachet, Olivier, Zeller, Marianne, Cottin, Yves, Vergely, Catherine
Format: Journal Article
Language:English
Published: England Elsevier Ltd 01.06.2015
Elsevier
Subjects:
Advanced Basic Science
Animals
anthracyclines
Anthracyclines - adverse effects
Anthracyclines - pharmacology
Antineoplastic Agents - adverse effects
Antineoplastic Agents - pharmacology
Cancer
Cardiology and cardiovascular system
Cardiotoxicity
Drug Synergism
Human health and pathology
Humans
Life Sciences
Myocytes, Cardiac - drug effects
Myocytes, Cardiac - metabolism
Oxidative Stress
Pharmaceutical sciences
Pharmacology
trastuzumab
Trastuzumab - adverse effects
Trastuzumab - pharmacology
trastuzumab
cardiotoxicity
anthracyclines
oxidative stress
ISSN:0165-6147, 1873-3735, 1873-3735
Online Access:Get full text
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Summary:•Anthracyclines and trastuzumab are effective chemotherapies that can cause cardiotoxicity.•Cardiotoxicity is due to a combination of ‘on-target’ and ‘off-target’ effects.•Neuregulin-1 in the microvascular endothelium is involved in cardiotoxicity.•ErbB2 could be a potential target for anticancer therapy.•Heme oxygenase-1 inhibition may be a strategy to enhance the response to chemotherapy.•Notch-1 is a novel target in trastuzumab-resistant breast cancer. Anticancer drugs continue to cause significant reductions in left ventricular ejection fraction resulting in congestive heart failure. The best-known cardiotoxic agents are anthracyclines (ANTHs) such as doxorubicin (DOX). For several decades cardiotoxicity was almost exclusively associated with ANTHs, for which cumulative dose-related cardiac damage was the use-limiting step. Human epidermal growth factor (EGF) receptor 2 (HER2; ErbB2) has been identified as an important target for breast cancer. Trastuzumab (TRZ), a humanized anti-HER2 monoclonal antibody, is currently recommended as first-line treatment for patients with metastatic HER2+ tumors. The use of TRZ may be limited by the development of drug intolerance, such as cardiac dysfunction. Cardiotoxicity has been attributed to free-iron-based, radical-induced oxidative stress. Many approaches have been promoted to minimize these serious side effects, but they are still clinically problematic. A new approach to personalized medicine for cancer that involves molecular screening for clinically relevant genomic alterations and genotype-targeted treatments is emerging.
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ISSN:0165-6147
1873-3735
1873-3735
DOI:10.1016/j.tips.2015.03.005