ERBB2 KD mutants bind TKIs

Stable Identifier
R-HSA-9665121
Type
Reaction [binding]
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
General
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Sensitivity to different tyrosine kinase inhibitors varies among ERBB2 mutants.

The following ERBB2 KD mutants are at least partially sensitive to lapatinib:
ERBB2 L755M (Nagano et al. 2018 - partial sensitivity);
ERBB2 D769H (Bose et al. 2013, Nagano et al. 2018);
ERBB2 V777L (Kancha et al. 2011, Bose et al. 2013, Nagano et al. 2018);
ERBB2 V777M (Nagano et al. 2018);
ERBB2 T862A (Kancha et al. 2011 - partial sensitivity, Nagano et al. 2018 - partial sensitivity);
ERBB2 H878Y (Kancha et al. 2011, Nagano et al. 2018);

The following ERBB2 KD mutants are at least partially sensitive to neratinib (HKI-272):
ERBB2 L755M (Nagano et al. 2018);
ERBB2 L755P (Nagano et al. 2018 - partial sensitivity);
ERBB2 L755S (Cocco et al. 2018; Nagano et al. 2018 - partial sensitivity);
ERBB2 I767M (Bose et al. 2013, Nagano et al. 2018);
ERBB2 D769H (Bose et al. 2013, Nagano et al. 2018);
ERBB2 D769Y (Bose et al. 2013, Nagano et al. 2018);
ERBB2 V777L (Bose et al. 2013, Nagano et al. 2018);
ERBB2 V777M (Nagano et al. 2018);
ERBB2 P780_Y781insGSP (Bose et al. 2013, Nagano et al. 2018, Ogoshi et al. 2018);
ERBB2 V842I (Bose et al. 2013, Nagano et al. 2018);
ERBB2 T862A (Nagano et al. 2018);
ERBB2 L869R (Hanker et al. 2017);
ERBB2 H878Y (Hu, Hu et al. 2015, Hu, Wan et al. 2015, Nagano et al. 2018);
ERBB2 R896C (Bose et al. 2013, Nagano et al. 2018);
ERBB2 L755_T759del (Bose et al. 2013);
ERBB2 A775_G776insYVMA (Minami et al. 2007)

The following ERBB2 KD mutants are at least partially sensitive to osimertinib:
ERBB2 L755M (Nagano et al. 2018);
ERBB2 L755P (Nagano et al. 2018);
ERBB2 L755S (Nagano et al. 2018);
ERBB2 I767M (Nagano et al. 2018);
ERBB2 D769H (Nagano et al. 2018);
ERBB2 D769Y (Nagano et al. 2018);
ERBB2 V777L (Nagano et al. 2018);
ERBB2 V777M (Nagano et al. 2018);
ERBB2 P780_Y781insGSP (Nagano et al. 2018 - partial response);
ERBB2 V842I (Nagano et al. 2018);
ERBB2 T862A (Nagano et al. 2018);
ERBB2 H878Y (Nagano et al. 2018);
ERBB2 R896C (Nagano et al. 2018);

The following ERBB2 KD mutants are at least partially sensitive to afatinib (BIBW2992):
ERBB2 L755M (Nagano et al. 2018);
ERBB2 L755P (Nagano et al. 2018 - partial sensitivity);
ERBB2 L755S (Nagano et al. 2018 - partial sensitivity);
ERBB2 D769H (Nagano et al. 2018);
ERBB2 D769Y (Nagano et al. 2018);
ERBB2 V777L (Nagano et al. 2018);
ERBB2 V777M (Nagano et al. 2018);
ERBB2 P780_Y781insGSP (Suzawa et al. 2016, Nagano et al. 2018)
ERBB2 T798I (Hanker et al. 2017);
ERBB2 V842I (Nagano et al. 2018);
ERBB2 T862A (Nagano et al. 2018);
ERBB2 L869R (Hanker et al. 2017);
ERBB2 H878Y (Hu, Wan et al. 2015, Nagano et al. 2018);
ERBB2 R896C (Nagano et al. 2018);

The following ERBB2 KD mutants are at least partially sensitive to AZ5104:
ERBB2 T798I (Hanker et al. 2017);
ERBB2 T798M (Hanker et al. 2017 – partial sensitivity);
ERBB2 L869R (Hanker et al. 2017);

The following ERBB2 KD mutants are at least partially sensitive to tesevatinib (EXEL-7647):
ERBB2 L755S (Trowe et al. 2008);
ERBB2 T798I (Trowe et al. 2008);

The following ERBB2 KD mutants are at least partially sensitive to canertinib (CI-1033):
ERBB2 H878Y (Hu, Wan et al. 2015);

The following ERBB2 KD mutants are at least partially sensitive to sapitinib:
ERBB2 L755M (Nagano et al. 2018 - partial sensitivity);
ERBB2 L755P (Nagano et al. 2018 - partial sensitivity);
ERBB2 L755S (Nagano et al. 2018 - partial sensitivity);
ERBB2 I767M (Nagano et al. 2018 - partial response);
ERBB2 D769H (Nagano et al. 2018);
ERBB2 D769Y (Nagano et al. 2018);
ERBB2 V777L (Nagano et al. 2018);
ERBB2 V777M (Nagano et al. 2018 - partial response);
ERBB2 P780_Y781insGSP (Nagano et al. 2018);
ERBB2 V842I (Nagano et al. 2018 - partial response);
ERBB2 H878Y (Nagano et al. 2018 - partial sensitivity)
ERBB2 R896C (Nagano et al. 2018 partial sensitivity);

The following ERBB2 KD mutants are at least partially sensitive to CP-724714:
ERBB2 H878Y (Hu, Wan et al. 2015);

The following ERBB2 KD mutants are at least partially sensitive to AEE788:
ERBB2 H878Y (Kancha et al. 2011; Hu, Wan et al. 2015);

The following ERBB2 KD mutants are at least partially sensitive to gefitinib
ERBB2 L755_T759del (Bose et al. 2013);

Literature References
PubMed ID Title Journal Year
17311002 The major lung cancer-derived mutants of ERBB2 are oncogenic and are associated with sensitivity to the irreversible EGFR/ERBB2 inhibitor HKI-272

Minami, Y, Shimamura, T, Shah, K, LaFramboise, T, Glatt, KA, Liniker, E, Borgman, CL, Haringsma, HJ, Feng, W, Weir, BA, Lowell, AM, Lee, JC, Wolf, J, Shapiro, GI, Wong, KK, Meyerson, M, Thomas, RK

Oncogene 2007
18413839 EXEL-7647 inhibits mutant forms of ErbB2 associated with lapatinib resistance and neoplastic transformation

Trowe, T, Boukouvala, S, Calkins, K, Cutler, RE, Fong, R, Funke, R, Gendreau, SB, Kim, YD, Miller, N, Woolfrey, JR, Vysotskaia, V, Yang, JP, Gerritsen, ME, Matthews, DJ, Lamb, P, Heuer, TS

Clin. Cancer Res. 2008
26375550 Tumor driven by gain-of-function HER2 H878Y mutant is highly sensitive to HER2 inhibitor

Hu, Z, Hu, Y, Liu, X, Xi, R, Zhang, A, Liu, D, Xie, Q, Chen, L

Oncotarget 2015
29967253 High-Throughput Functional Evaluation of Variants of Unknown Significance in ERBB2

Nagano, M, Kohsaka, S, Ueno, T, Kojima, S, Saka, K, Iwase, H, Kawazu, M, Mano, H

Clin. Cancer Res. 2018
22046346 Differential sensitivity of ERBB2 kinase domain mutations towards lapatinib

Kancha, RK, von Bubnoff, N, Bartosch, N, Peschel, C, Engh, RA, Duyster, J

PLoS ONE 2011
30854046 Anti-tumor effect of neratinib against lung cancer cells harboring HER2 oncogene alterations

Ogoshi, Y, Shien, K, Yoshioka, T, Torigoe, H, Sato, H, Sakaguchi, M, Tomida, S, Namba, K, Kurihara, E, Takahashi, Y, Suzawa, K, Yamamoto, H, Soh, J, Toyooka, S

Oncol Lett 2019
26545934 Antitumor effect of afatinib, as a human epidermal growth factor receptor 2-targeted therapy, in lung cancers harboring HER2 oncogene alterations

Suzawa, K, Toyooka, S, Sakaguchi, M, Morita, M, Yamamoto, H, Tomida, S, Ohtsuka, T, Watanabe, M, Hashida, S, Maki, Y, Soh, J, Asano, H, Tsukuda, K, Miyoshi, S

Cancer Sci. 2016
25853726 Phosphorylation of mutationally introduced tyrosine in the activation loop of HER2 confers gain-of-function activity

Hu, Z, Wan, X, Hao, R, Zhang, H, Li, L, Li, L, Xie, Q, Wang, P, Gao, Y, Chen, S, Wei, M, Luan, Z, Zhang, A, Huang, N, Chen, L

PLoS ONE 2015
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
23220880 Activating HER2 mutations in HER2 gene amplification negative breast cancer

Bose, R, Kavuri, SM, Searleman, AC, Shen, W, Shen, D, Koboldt, DC, Monsey, J, Goel, N, Aronson, AB, Li, S, Ma, CX, Ding, L, Mardis, ER, Ellis, MJ

Cancer Discov 2013
Participants
Participant Of
Disease
Name Identifier Synonyms
cancer 162 malignant tumor, malignant neoplasm, primary cancer
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