Anthracyclines/trastuzumab: new aspects of cardiotoxicity and molecular mechanisms

Trends Pharmacol Sci. 2015 Jun;36(6):326-48. doi: 10.1016/ Epub 2015 Apr 17.


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.

Keywords: anthracyclines; cardiotoxicity; oxidative stress; trastuzumab.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Anthracyclines / adverse effects*
  • Anthracyclines / pharmacology
  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / pharmacology
  • Cardiotoxicity
  • Drug Synergism
  • Humans
  • Myocytes, Cardiac / drug effects
  • Myocytes, Cardiac / metabolism
  • Oxidative Stress
  • Trastuzumab / adverse effects*
  • Trastuzumab / pharmacology


  • Anthracyclines
  • Antineoplastic Agents
  • Trastuzumab