Laboratoire de Physiopathologie et Pharmacologie Cardio-métaboliques (LPPCM), Institut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche 866, Facultés de Médecine et de Pharmacie - Université de Bourgogne, 7 Boulevard Jeanne d'Arc, 21033 Dijon, France.
Laboratoire de Physiopathologie et Pharmacologie Cardio-métaboliques (LPPCM), Institut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche 866, Facultés de Médecine et de Pharmacie - Université de Bourgogne, 7 Boulevard Jeanne d'Arc, 21033 Dijon, France; Service de Cardiologie, Centre Hospitalier Universitaire Bocage, Dijon, France.
Trends Pharmacol Sci. 2015 Jun;36(6):326-48. doi: 10.1016/j.tips.2015.03.005. 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.
抗癌药物继续导致左心室射血分数显著降低，导致充血性心力衰竭。最著名的心脏毒性药物是蒽环类药物（ANTHs），如多柔比星（DOX）。几十年来，心脏毒性几乎完全与 ANTHs 相关，其累积剂量相关的心脏损伤是使用的限制步骤。人表皮生长因子受体 2（HER2；ErbB2）已被确定为乳腺癌的一个重要靶点。曲妥珠单抗（TRZ），一种人源化抗 HER2 单克隆抗体，目前被推荐用于转移性 HER2（+）肿瘤患者的一线治疗。TRZ 的使用可能会受到药物不耐受的限制，例如心脏功能障碍。心脏毒性归因于基于游离铁的、自由基诱导的氧化应激。已经提出了许多方法来最小化这些严重的副作用，但它们在临床上仍然是有问题的。一种新的癌症个体化医学方法正在出现，涉及针对临床相关基因组改变的分子筛选和基于基因型的治疗。
