Herceptin, a recombinant humanized anti-ERBB2 monoclonal antibody, induces cardiomyocyte death

► Trastuzumab (Herceptin®) and the rat ERBB2/HER2/NEU antibody elevate p53 protein levels, enhances apoptosis, increases cleaved caspase-3 levels and diminishes cardiac function. ► The adverse cardiac events observed with trastuzumab may stem from its negative regulation of MDM2 events which impairs p53 degradation resultantly promoting apoptosis leading to cardiac dysfunction. ► These observations suggest that anticancer agents that inhibit MDM2 and its downstream actions may curb tumor progression at the expense of increasing cardiac stress.