Resistant ERBB2 KD mutants do not bind trastuzumab

Stable Identifier
Reaction [transition]
Homo sapiens
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The following ERBB2 KD mutants are resistant to the therapeutic antibody trastuzumab (herceptin):

ERBB2 L755P (Nagano et al. 2018);
ERBB2 L755S (Nagano et al. 2018);
ERBB2 I767M (Bose et al. 2013);
ERBB2 D769Y (Nagano et al. 2018);
ERBB2 V777L (Nagano et al. 2018);
ERBB2 G778_P780dup (Bose et al. 2013, Nagano et al. 2018);
ERBB2 T798M (Rexer et al. 2013);
ERBB2 V842I (Nagano et al. 2018);
ERBB2 T862A (Nagano et al. 2018);
ERBB2 L869R (Hanker et al. 2017);

For ERBB2 R896C, both resistance (Bose et al. 2013) and sensitivity (Nagano et al. 2018) to trastuzumab have been reported.
Literature References
PubMed ID Title Journal Year
29967253 High-Throughput Functional Evaluation of Variants of Unknown Significance in ERBB2

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

Clin. Cancer Res. 2018
28274957 An Acquired HER2T798I Gatekeeper Mutation Induces Resistance to Neratinib in a Patient with HER2 Mutant-Driven Breast Cancer

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

Cancer Discov 2017
23948973 Human breast cancer cells harboring a gatekeeper T798M mutation in HER2 overexpress EGFR ligands and are sensitive to dual inhibition of EGFR and HER2

Song, Y, Estrada, MV, Arteaga, CL, Chakrabarty, A, Narasanna, A, Ghosh, R, Rexer, BN, Engelman, JA

Clin. Cancer Res. 2013
23220880 Activating HER2 mutations in HER2 gene amplification negative breast cancer

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

Cancer Discov 2013
Normal reaction
Functional status

Loss of function of ERBB2 KD mutants (trastuzumab resistant):ERBIN:HSP90:CDC37 [plasma membrane]

Name Identifier Synonyms
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
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