ERBB2 and breast carcinoma: We speculate as a possible explanation for the remarkable inhibitory activity of SMET2.1Fc against HER2-overexpressing human breast cancer cells that because of the unique conserved epitope of SMET2.1 and the shorter distance between two antigen-binding sites of dAb-Fc compared to IgG1, cell-surface HER2 molecules could be locked into a rigid homodimer structure that results in systemic inhibition of HER2-mediated tumorigenic signaling pathways (Figure 7).