ERBB2 binds trastuzumab

Stable Identifier
R-HSA-9652277
Type
Reaction [binding]
Species
Homo sapiens
Compartment
extracellular region, plasma membrane
ReviewStatus
5/5
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ERBB2 binds trastuzumab
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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).
Literature References
PubMed ID Title Journal Year
1350088 Humanization of an anti-p185HER2 antibody for human cancer therapy

Carter, P, Presta, L, Gorman, CM, Ridgway, JB, Henner, D, Wong, WL, Rowland, AM, Kotts, C, Carver, ME, Shepard, HM

Proc. Natl. Acad. Sci. U.S.A. 1992
29490608 The effects of trastuzumab on HER2-mediated cell signaling in CHO cells expressing human HER2

Maadi, H, Nami, B, Tong, J, Li, G, Wang, Z

BMC Cancer 2018
2566907 p185HER2 monoclonal antibody has antiproliferative effects in vitro and sensitizes human breast tumor cells to tumor necrosis factor

Hudziak, RM, Lewis, GD, Winget, M, Fendly, BM, Shepard, HM, Ullrich, A

Mol. Cell. Biol. 1989
Participants
Input
Output
Participates
as an event of
Disease
Name Identifier Synonyms
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
Cross References
Mondo
Authored
Orlic-Milacic, M  (2019-07-31)
Reviewed
Kancha, RK  (2019-09-16)
Created
Orlic-Milacic, M  (2019-06-28)
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