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Cardiotoxicity is a common and potentially devastating side effect of antineoplastic drug therapy. This empiric observation is seen as paradoxical given that the cardiomyocyte is considered to be a terminally differentiated cell. Despite the fact that these cells do not divide after birth, adult cardiomyocytes may become “innocent bystander” targets of anticancer drugs designed to interfere with cell signaling pathways in rapidly proliferating cells. In breast cancer clinical trials, treatment with the erbB2 receptor antibody trastuzumab combined with anthracyclines has been associated with an increased risk for the development of cardiac pump failure. Trastuzumab/anthracycline cardiomyopathy may be the first clinically significant cardiotoxicity to emerge from signal transduction therapeutics. The erbB2 receptor tyrosine kinase is known to have a critical role in cardiac development. In addition, erbB2 is thought to participate …