Mechanism of action of trastuzumab and scientific update.

The humanized anti-p185(HER2) monoclonal antibody trastuzumab has been shown to effectively inhibit the growth of HER2-overexpressing breast cancer cells in vivo and in vitro. The treatment of cancer cells with trastuzumab results in downregulation of the HER2 receptor. Further downstream cellular events include the accumulation of the cyclin-dependent kinase inhibitor p27 and cell cycle arrest. In vivo, trastuzumab induces antibody-dependent cellular cytotoxicity. Trastuzumab also inhibits constitutive HER2 cleavage/shedding mediated by metalloproteases. The ability of trastuzumab to inhibit HER2 cleavage may correlate with the clinical anticancer activity of the multifunctional HER2-targeting antibody. Copyright 2001 by W.B. Saunders Company.