Interesting excerpt from the New England J Med about Herceptin and the heart with AC

[RobinP]

http://content.nejm.org/cgi/content/...uery=nextarrow

Herceptin and the Heart — Kenneth R. Chien, M.D., Ph.D


Clinical studies support the concept that trastuzumab acts as a molecular modifier of anthracycline-induced cardiotoxic effects and associated heart failure (Panel B). Panel C shows the proposed pathway by which trastuzumab modifies anthracycline cardiotoxicity. In response to a variety of pathological stimuli causing biomechanical stress, including exposure to anthracyclines, pathways leading to the death of cardiomyocytes are activated. The irreversible loss of viable cardiac muscle is normally prevented by the concomitant activation of cardiomyocyte-survival pathways, including gp130 cytokines and neuregulin. Trastuzumab, by inhibiting the ErbB2 receptor, leads to a loss of the neuregulin-dependent pathways that result in the survival of cardiac myocytes. In most patients, the activation of other survival pathways is sufficient to prevent the loss of viable muscle cells and the onset of heart failure. However, in a subgroup of patients, the loss of the ErbB2-dependent survival pathways promotes the cardiotoxic effects of anthracyclines. Adapted from Chien1 and Crone et al.2 LIFR denotes leukemia inhibitory factor receptor.