Drug-mediated inhibition of ERBB2 signaling

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Homo sapiens
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Signaling by ERBB2 can be pharmacologically inhibited with tyrosine kinase inhibitors (TKIs) (Nelson and Fry 2001, Xia et al. 2002, Wood et al. 2004, Rabindran et al. 2004, Gandreau et al. 2007, Jani et al. 2007, Li et al. 2008, Hichkinson et al. 2010, Traxler et al. 2014, Hanker et al. 2017), and therapeutic antibodies, such as trastuzumab (Hudziak et al. 1989, Carter et al. 1992, Pickl and Ries 2009, Maadi et al. 2018) and pertuzumab (Franklin et al. 2004).

Literature References
PubMed ID Title Journal Year
12214266 Anti-tumor activity of GW572016: a dual tyrosine kinase inhibitor blocks EGF activation of EGFR/erbB2 and downstream Erk1/2 and AKT pathways

Xia, W, Mullin, RJ, Keith, BR, Liu, LH, Ma, H, Rusnak, DW, Owens, G, Alligood, KJ, Spector, NL

Oncogene 2002
17575237 Inhibition of the T790M gatekeeper mutant of the epidermal growth factor receptor by EXEL-7647

Gendreau, SB, Ventura, R, Keast, P, Laird, AD, Yakes, FM, Zhang, W, Bentzien, F, Cancilla, B, Lutman, J, Chu, F, Jackman, L, Shi, Y, Yu, P, Wang, J, Aftab, DT, Jaeger, CT, Meyer, SM, De Costa, A, Engell, K, Chen, J, Martini, JF, Joly, AH

Clin. Cancer Res. 2007
15093539 Insights into ErbB signaling from the structure of the ErbB2-pertuzumab complex

Franklin, MC, Carey, KD, Vajdos, FF, Leahy, DJ, de Vos, AM, Sliwkowski, MX

Cancer Cell 2004
20145185 AZD8931, an equipotent, reversible inhibitor of signaling by epidermal growth factor receptor, ERBB2 (HER2), and ERBB3: a unique agent for simultaneous ERBB receptor blockade in cancer

Hickinson, DM, Klinowska, T, Speake, G, Vincent, J, Trigwell, C, Anderton, J, Beck, S, Marshall, G, Davenport, S, Callis, R, Mills, E, Grosios, K, Smith, P, Barlaam, B, Wilkinson, RW, Ogilvie, D

Clin. Cancer Res. 2010
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
18408761 BIBW2992, an irreversible EGFR/HER2 inhibitor highly effective in preclinical lung cancer models

Li, D, Ambrogio, L, Shimamura, T, Kubo, S, Takahashi, M, Chirieac, LR, Padera, RF, Shapiro, GI, Baum, A, Himmelsbach, F, Rettig, WJ, Meyerson, M, Solca, F, Greulich, H, Wong, KK

Oncogene 2008
11278435 Akt, MAPK (Erk1/2), and p38 act in concert to promote apoptosis in response to ErbB receptor family inhibition

Nelson, JM, Fry, DW

J. Biol. Chem. 2001
15374980 A unique structure for epidermal growth factor receptor bound to GW572016 (Lapatinib): relationships among protein conformation, inhibitor off-rate, and receptor activity in tumor cells

Wood, ER, Truesdale, AT, McDonald, OB, Yuan, D, Hassell, A, Dickerson, SH, Ellis, B, Pennisi, C, Horne, E, Lackey, K, Alligood, KJ, Rusnak, DW, Gilmer, TM, Shewchuk, L

Cancer Res. 2004
15256466 AEE788: a dual family epidermal growth factor receptor/ErbB2 and vascular endothelial growth factor receptor tyrosine kinase inhibitor with antitumor and antiangiogenic activity

Traxler, P, Allegrini, PR, Brandt, R, Brueggen, J, Cozens, R, Fabbro, D, Grosios, K, Lane, HA, McSheehy, P, Mestan, J, Meyer, T, Tang, C, Wartmann, M, Wood, J, Caravatti, G

Cancer Res. 2004
18978815 Comparison of 3D and 2D tumor models reveals enhanced HER2 activation in 3D associated with an increased response to trastuzumab

Pickl, M, Ries, CH

Oncogene 2009
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
17942920 Discovery and pharmacologic characterization of CP-724,714, a selective ErbB2 tyrosine kinase inhibitor

Jani, JP, Finn, RS, Campbell, M, Coleman, KG, Connell, RD, Currier, N, Emerson, EO, Floyd, E, Harriman, S, Kath, JC, Morris, J, Moyer, JD, Pustilnik, LR, Rafidi, K, Ralston, S, Rossi, AM, Steyn, SJ, Wagner, L, Winter, SM, Bhattacharya, SK

Cancer Res. 2007
28274957 An Acquired HER2T798I Gatekeeper Mutation Induces Resistance to Neratinib in a Patient with HER2 Mutant-Driven Breast Cancer

Hanker, AB, Brewer, MR, Sheehan, JH, Koch, JP, Sliwoski, GR, Nagy, R, Lanman, R, Berger, MF, Hyman, DM, Solit, DB, He, J, Miller, V, Cutler, RE, Lalani, AS, Cross, D, Lovly, CM, Meiler, J, Arteaga, CL

Cancer Discov 2017
15173008 Antitumor activity of HKI-272, an orally active, irreversible inhibitor of the HER-2 tyrosine kinase

Rabindran, SK, Discafani, CM, Rosfjord, EC, Baxter, M, Floyd, MB, Golas, J, Hallett, WA, Johnson, BD, Nilakantan, R, Overbeek, E, Reich, MF, Shen, R, Shi, X, Tsou, HR, Wang, YF, Wissner, A

Cancer Res 2004
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