The anti-HER2 monoclonal antibody trastuzumab works by binding to subdomain IV of the HER2 extracellular domain, thereby blocking HER2 cleavage; stimulating antibody-dependent, cell-mediated cytotoxicity; and preventing ligand-independent, HER2- mediated mitogenic signaling. Pertuzumab is an anti- HER2 monoclonal antibody that binds to subdomain II of the HER2 extracellular domain, preventing HER2 from dimerizing with other ligand-activated HER receptors; like trastuzumab, pertuzumab also stimulates antibodydependent cell-mediated cytotoxicity. Pertuzumab’s binding at a different HER2 epitope than trastuzumab represents a complementary mechanism of action that provides more comprehensive inhibition of HER2 signaling when the two agents are used together; the combination has been shown to produce greater antitumor activity than either agent alone in HER2-positive tumor models...
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