Article ID Journal Published Year Pages File Type
2572596 Trends in Pharmacological Sciences 2015 23 Pages PDF
Abstract

•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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