期刊
TRENDS IN PHARMACOLOGICAL SCIENCES
卷 36, 期 6, 页码 326-348出版社
ELSEVIER SCIENCE LONDON
DOI: 10.1016/j.tips.2015.03.005
关键词
cardiotoxicity; anthracyclines; trastuzumab; oxidative stress
资金
- French Ministry of Research
- Institut National de la Sante et de la Recherche Medicale (INSERM)
- Regional Council of Burgundy (Conseil Regional de Bourgogne)
- Fonds Europeen de Developpement Regional (FEDER)
- Association de Cardiologie de Bourgogne
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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