Azim Hamdy, Azim Hatem A, Escudier Bernard
Department of Clinical Oncology, Cairo University Hospital, Cairo, Egypt.
Cancer Treat Rev. 2009 Nov;35(7):633-8. doi: 10.1016/j.ctrv.2009.06.007. Epub 2009 Jul 28.
HER2 gene plays a pivotal role in the pathogenesis of 20% of breast cancer patients. At the same time, it is one of the main cardiac survival pathways when subjected to bio-mechanical stress including exposure to anthracyclines. With the emergence of the anti-HER2 targeting agents, concerns raised regarding the potential cardiac toxicities of these drugs. In the early clinical trials with trastuzumab, it was evident that it has a significant cardiac toxicity. The incidence of symptomatic heart failure ranged from 4% to 7% with trastuzumab alone, and 27% when administered concurrently with doxorubicin. On the other hand, available data suggest that lapatinib is much less cardiotoxic. The incidence of symptomatic heart failure has been constantly reported to be less than 0.5%. In this review, we discuss the possible theories behind the differences in the cardiac profile of both agents. We emphasize on the role of cardiac bioenergetics and the effects of trastuzumab and lapatinib on ATP production through the different effects they exert on the cardiac mitochondria.
HER2基因在20%的乳腺癌患者发病机制中起关键作用。同时，当受到包括接触蒽环类药物在内的生物力学应激时，它是主要的心脏存活途径之一。随着抗HER2靶向药物的出现，人们对这些药物潜在的心脏毒性产生了担忧。在曲妥珠单抗的早期临床试验中，明显发现它具有显著的心脏毒性。单独使用曲妥珠单抗时，有症状心力衰竭的发生率为4%至7%，与多柔比星同时使用时为27%。另一方面，现有数据表明拉帕替尼的心脏毒性要小得多。有症状心力衰竭的发生率一直报告低于0.5%。在本综述中，我们讨论了两种药物心脏特征差异背后的可能理论。我们强调心脏生物能量学的作用以及曲妥珠单抗和拉帕替尼通过对心脏线粒体的不同作用对ATP产生的影响。
