Anthracyclines/trastuzumab: new aspects of cardiotoxicity and molecular mechanisms

作者：Rochette Luc^*; Guenancia Charles; Gudjoncik Aurelie; Hachet Olivier; Zeller Marianne; Cottin Yves; Vergely Catherine

来源：Trends in Pharmacological Sciences, 2015, 36(6): 326-348.

DOI：10.1016/j.tips.2015.03.005

• cardiotoxicity
• anthracyclines
• trastuzumab
• oxidative stress

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.

• 出版日期2015-6