alectinib resistant ALK mutants don't bind alectinib

Stable Identifier
R-HSA-9700656
Type
Reaction [transition]
Species
Homo sapiens
Compartment
cytosol, plasma membrane
ReviewStatus
5/5
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alectinib resistant ALK mutants don't bind alectinib
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The following ALK mutants show resistance to alectinib:

ALK L1122V: Ceccon et al, 2015
ALK I1171N: Toyokawa et al, 2014; Ou et al, 2014; Gainor et al, 2016
ALK I1171S: Gainor et al 2016; Ou et al, 2014; Ou et al, 2016
ALK I1171T: Gainor et al, 2016; Ou et al, 2014; Zdzalik et al, 2014; Katayama et al, 2014
ALK F1174C: Ou et al, 2016
ALK V1180L: Katayama et al, 2014
ALK L1196M: Ceccon et al, 2015 (moderate); Gainor et al, 2016
ALK L1198F: Ceccon et al, 2015
ALK G1202R: Makimoto et al, 2019; Lin et al, 2016; Gainor et al, 2016
ALK S1206C: Ceccon et al, 2015

Literature References
PubMed ID Title Journal Year
25228534 Two novel ALK mutations mediate acquired resistance to the next-generation ALK inhibitor alectinib

Katayama, R, Friboulet, L, Koike, S, Lockerman, EL, Khan, TM, Gainor, JF, Iafrate, AJ, Takeuchi, K, Taiji, M, Okuno, Y, Fujita, N, Engelman, JA, Shaw, AT

Clin Cancer Res 2014
24509625 Activating mutations in ALK kinase domain confer resistance to structurally unrelated ALK inhibitors in NPM-ALK-positive anaplastic large-cell lymphoma

Zdzalik, D, Dymek, B, Grygielewicz, P, Gunerka, P, Bujak, A, Lamparska-Przybysz, M, Wieczorek, M, Dzwonek, K

J Cancer Res Clin Oncol 2014
31374369 Rapid Acquisition of Alectinib Resistance in ALK-Positive Lung Cancer With High Tumor Mutation Burden

Makimoto, G, Ohashi, K, Tomida, S, Nishii, K, Matsubara, T, Kayatani, H, Higo, H, Ninomiya, K, Sato, A, Watanabe, H, Kano, H, Ninomiya, T, Kubo, T, Rai, K, Ichihara, E, Hotta, K, Tabata, M, Toyooka, S, Takata, M, Maeda, Y, Kiura, K

J Thorac Oncol 2019
26464158 ALK F1174V mutation confers sensitivity while ALK I1171 mutation confers resistance to alectinib. The importance of serial biopsy post progression

Ou, SH, Milliken, JC, Azada, MC, Miller, VA, Ali, SM, Klempner, SJ

Lung Cancer 2016
25393798 Secondary mutations at I1171 in the ALK gene confer resistance to both Crizotinib and Alectinib

Toyokawa, G, Hirai, F, Inamasu, E, Yoshida, T, Nosaki, K, Takenaka, T, Yamaguchi, M, Seto, T, Takenoyama, M, Ichinose, Y

J Thorac Oncol 2014
27432227 Molecular Mechanisms of Resistance to First- and Second-Generation ALK Inhibitors in ALK-Rearranged Lung Cancer

Gainor, JF, Dardaei, L, Yoda, S, Friboulet, L, Leshchiner, I, Katayama, R, Dagogo-Jack, I, Gadgeel, S, Schultz, K, Singh, M, Chin, E, Parks, M, Lee, D, DiCecca, RH, Lockerman, E, Huynh, T, Logan, J, Ritterhouse, LL, Le, LP, Muniappan, A, Digumarthy, S, Channick, C, Keyes, C, Getz, G, Dias-Santagata, D, Heist, RS, Lennerz, J, Sequist, LV, Benes, CH, Iafrate, AJ, Mino-Kenudson, M, Engelman, JA, Shaw, AT

Cancer Discov 2016
25421750 Treatment Efficacy and Resistance Mechanisms Using the Second-Generation ALK Inhibitor AP26113 in Human NPM-ALK-Positive Anaplastic Large Cell Lymphoma

Ceccon, M, Mologni, L, Giudici, G, Piazza, R, Pirola, A, Fontana, D, Gambacorti-Passerini, C

Mol. Cancer Res. 2015
25393796 Identification of a novel HIP1-ALK fusion variant in Non-Small-Cell Lung Cancer (NSCLC) and discovery of ALK I1171 (I1171N/S) mutations in two ALK-rearranged NSCLC patients with resistance to Alectinib

Ou, SH, Klempner, SJ, Greenbowe, JR, Azada, M, Schrock, AB, Ali, SM, Ross, JS, Stephens, PJ, Miller, VA

J Thorac Oncol 2014
27130468 Anaplastic Lymphoma Kinase (ALK) Kinase Domain Mutation Following ALK Inhibitor(s) Failure in Advanced ALK Positive Non-Small-Cell Lung Cancer: Analysis and Literature Review

Lin, YT, Yu, CJ, Yang, JC, Shih, JY

Clin Lung Cancer 2016
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Normal reaction
Liganded-ALK dimer binds type I ALK-binding TKIs (Homo sapiens)
Functional status

Loss of function of alectinib resistant ALK mutants [plasma membrane]

Normal Entity
Disease Entity
Status
Disease
Name Identifier Synonyms
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
Cross References
Mondo
Authored
Rothfels, K  (2021-03-22)
Reviewed
Inghirami, G  (2021-05-04)
Created
Rothfels, K  (2020-09-16)
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