ERBB2 signaling is inhibited by binding of ERBB2 to ERBB2-directed therapeutic recombinant antibody trastuzumab (herceptin), used an anti-cancer therapeutic in tumors that overexpress ERBB2 (Hudziak et al. 1989, Carter et al. 1992). Trastuzumab does not prevent homodimerization of overexpressed ERBB2 and remains bound to ERBB2 (HER2) homodimers (Maadi et al. 2018). Autophosphorylation of ERBB2 homodimers and downstream signaling is inhibited by trastuzumab (Pickl and Ries 2009). It is unclear whether trastuzumab mainly acts through endocytosis-mediated downregulation of ERBB2 receptor on the cell surface or through interference with the kinase activity. The mechanism of trastuzumab action may also rely on antibody-dependent cellular cytotoxicity (ADCC) (Maadi et al. 2008).
Maadi, H, Nami, B, Tong, J, Li, G, Wang, Z
Carter, P, Presta, L, Gorman, CM, Ridgway, JB, Henner, D, Wong, WL, Rowland, AM, Kotts, C, Carver, ME, Shepard, HM
Hudziak, RM, Lewis, GD, Winget, M, Fendly, BM, Shepard, HM, Ullrich, A
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