crizotinib-resistant ALK mutants don't bind crizotinib

Stable Identifier
R-HSA-9715357
Type
Reaction [FailedReaction]
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
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The following ALK mutants show resistance to inhibition by crizotinib:

ALK L1122V: Ceccon et al, 2015 (moderate)
ALK T1151InsT: Katayama et al, 2012
ALK T1151M: Noe et al, 2020
ALK L1152R: Sasaki et al, 2011
ALK C1156Y: Noe et al, 2020; Saber et al 2016; Huang et al, 2013; Choi et al, 2010; Gainor et al, 2016
ALK I1171N: Gainor et al, 2016; Zhang et al, 2011; Ceccon et al, 2013
ALK I1171S: Gainor et al, 2016; Zhang et al, 2011
ALK I1171T: Noe et al, 2020; Toyokawa et al, 2014; Gainor et al, 2016; Zhang et al, 2011; Zdzalik et al, 2014; Katayama et al, 2014
ALK F1174C: Noe et al, 2020; Friboulet et al, 2014
ALK F1174L: Noe et al, 2020; Sasaki et al, 2010; Heuckmann et al, 2011
ALK F1174V: Noe et al, 2020; Ou et al, 2014
ALK V1180L: Katayama et al, 2014
ALK L1196M: Gainor et al, 2016; Huang et al, 2013; Katayama et al, 2012; Kim et al, 2013; Choi et al, 2010; Doebele et al, 2012; Friboulet et al, 2014; Heuckmann et al, 2011; Huang et al, 2013
ALK L1196Q: Ceccon et al, 2013
ALK L1198P: Heuckmann et al, 2011
ALK G1202R: Katayama et al, 2012; Noe et al, 2020; Kougiomtzi et al, 2019; Gainor et al, 2016, Ou et al, 2016; Chuang et al, 2019
ALK D1203N: Heuckmann et al, 2011
ALK S1206C: Ceccon et al, 2015
ALK S1206F: Noe et al, 2020
ALK S1206Y: Gainor et al, 2016; Friboulet et al, 2014; Katayama et al, 2012; Noe et al, 2020
ALK G1228A: Ai et al, 2018
ALK G1269A: Noe et al, 2020; Saber et al, 2016; Gainor et al, 2016; Friboulet et al, 2014; Huang et al, 2013; Kim et al, 2013; Xu et al, 2019; Doebele et al, 2012; Heuckmann et al, 2011; Amin et al, 2016
ALK G1269S: Heuckmann et al, 2011

Literature References
PubMed ID Title Journal Year
31712133 ALK Mutation Status Before and After Alectinib Treatment in Locally Advanced or Metastatic ALK-Positive NSCLC: Pooled Analysis of Two Prospective Trials

Shaw, AT, Yaung, SJ, Ou, SI, Noe, J, Bordogna, W, Cummings, CA, Klass, DM, Lovejoy, A

J Thorac Oncol 2020
25393798 Secondary mutations at I1171 in the ALK gene confer resistance to both Crizotinib and Alectinib

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

J Thorac Oncol 2014
21948233 ALK mutations conferring differential resistance to structurally diverse ALK inhibitors

Lovly, CM, Grütter, C, Heynck, S, Sos, ML, Thomas, RK, Peifer, M, Balke-Want, H, Heuckmann, JM, Rauh, D, Koker, M, Weiss, J, Pao, W, Hölzel, M

Clin. Cancer Res. 2011
22277784 Mechanisms of acquired crizotinib resistance in ALK-rearranged lung Cancers

Saeh, JC, Mino-Kenudson, M, Iafrate, AJ, Solomon, BJ, Jessop, NA, Crosby, K, Shaw, AT, Halmos, B, Engelman, JA, Khan, TM, Drew, L, Wain, JC, Sequist, LV, Yeo, AT, Benes, C, Katayama, R

Sci Transl Med 2012
30089600 Next generation sequencing reveals a novel ALK G1128A mutation resistant to crizotinib in an ALK-Rearranged NSCLC patient

Ou, SI, Lu, S, Chang, L, Niu, X, Chen, R, Ai, X

Lung Cancer 2018
27045755 Genomic Aberrations in Crizotinib Resistant Lung Adenocarcinoma Samples Identified by Transcriptome Sequencing

Bosman, LJ, van den Berg, A, Timens, W, Mastik, MF, Kok, K, Schuuring, E, Groen, HJ, Terpstra, MM, Hiltermann, TJ, Saber, A, van der Wekken, AJ

PLoS One 2016
20979473 EML4-ALK mutations in lung cancer that confer resistance to ALK inhibitors

Ishikawa, Y, Soda, M, Ueno, T, Choi, YL, Yamashita, Y, Kimura, H, Takashima, J, Tanio, Y, Nakajima, T, Hamada, T, ALK Lung Cancer Study Group, -, Mitsudomi, T, Yatabe, Y, Haruta, H, Takeuchi, K, Mano, H

N. Engl. J. Med. 2010
24675041 The ALK inhibitor ceritinib overcomes crizotinib resistance in non-small cell lung cancer

Sun, F, Crystal, AS, Awad, MM, Li, N, Friboulet, L, Michellys, PY, Kasibhatla, S, Lee, CC, Shaw, AT, Li, J, Harris, JL, Engelman, JA, Kim, S, Lockerman, EL, Yanagitani, N, Mahmood, S, Nishio, M, McNamara, P, Pferdekamper, AC, Hua, S, Fujita, N, Gainor, JF, Sun, X, Katayama, R

Cancer Discov 2014
21030459 The neuroblastoma-associated F1174L ALK mutation causes resistance to an ALK kinase inhibitor in ALK-translocated cancers

Shapiro, GI, Jänne, PA, Rodig, SJ, Eck, MJ, Demetri, G, Sasaki, T, Okuda, K, Wilner, K, Butrynski, J, Zheng, W, Capelletti, M, Wang, L, Gray, NS, Christensen, JG

Cancer Res 2010
27432227 Molecular Mechanisms of Resistance to First- and Second-Generation ALK Inhibitors in ALK-Rearranged Lung Cancer

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

Cancer Discov 2016
23434628 Multiplexed deep sequencing analysis of ALK kinase domain identifies resistance mutations in relapsed patients following crizotinib treatment

Mao, M, Lee, NV, Lira, P, Kim, DW, Sun, JM, Ho, SN, Park, K, Vizcarra, P, Kotsakis, A, Huang, D, Cao, JQ, Ahn, MJ, Deng, S, Ahn, JS, Kim, TM, Christensen, JG

Genomics 2013
21791641 A novel ALK secondary mutation and EGFR signaling cause resistance to ALK kinase inhibitors

Zheng, W, Lindeman, N, Capelletti, M, Gray, NS, Wong, KK, Christensen, JG, Ercan, D, Jänne, PA, Rodig, SJ, Shimamura, T, Nikiforow, S, Weremowicz, S, Sasaki, T, Okuda, K, Wilner, K, Eck, MJ, Butaney, M, Stumpfova, M, Yanagita, M, Heon, S, Ogino, A, Xiao, Y, Marcoux, JP, Koivunen, J, Lathan, C, Du, J

Cancer Res. 2011
23239810 Crizotinib-resistant NPM-ALK mutants confer differential sensitivity to unrelated Alk inhibitors

Ceccon, M, Mologni, L, Scapozza, L, Bisson, W, Gambacorti-Passerini, C

Mol. Cancer Res. 2013
30675302 ALK-G1269A mutation in epithelioid inflammatory myofibroblastic sarcoma after progression on crizotinib: A case report

Liu, T, Yu, Y, Li, H, Xu, X, Hou, Y, Peng, K, Sun, Y, Fang, Y, Chen, L

Oncol Lett 2019
21502504 Therapeutic strategies to overcome crizotinib resistance in non-small cell lung cancers harboring the fusion oncogene EML4-ALK

Khan, TM, Iafrate, AJ, Shakespeare, WC, Shaw, AT, Lifshits, E, Rivera, VM, Ebi, H, Engelman, JA, Benes, C, Katayama, R

Proc. Natl. Acad. Sci. U.S.A. 2011
22235099 Mechanisms of resistance to crizotinib in patients with ALK gene rearranged non-small cell lung cancer

Kondo, KL, Le, AT, Linderman, DJ, Aisner, DL, Heasley, LE, Kutateladze, TG, Doebele, RC, Franklin, WA, Varella-Garcia, M, Pilling, AB, Weickhardt, AJ, Camidge, DR

Clin. Cancer Res. 2012
24736079 Next-generation sequencing reveals a Novel NSCLC ALK F1174V mutation and confirms ALK G1202R mutation confers high-level resistance to alectinib (CH5424802/RO5424802) in ALK-rearranged NSCLC patients who progressed on crizotinib

Azada, M, Ignatius Ou, SH, Klempner, SJ, Herman, JM, Ali, SM, He, J, Casey, C, Siwak-Tapp, C, Miller, VA, Hsiang, DJ, Kain, TS

J Thorac Oncol 2014
23344087 Heterogeneity of genetic changes associated with acquired crizotinib resistance in ALK-rearranged lung cancer

Chung, DH, Lee, SH, Go, H, Heo, DS, Keam, B, Kim, DW, Kim, S, Kim, TM, Ku, JL

J Thorac Oncol 2013
31749991 Molecular findings reveal possible resistance mechanisms in a patient with ALK-rearranged lung cancer: a case report and literature review

Kampletsas, E, Ntellas, P, Nasioulas, G, Papadopoulou, E, Kougioumtzi, A, Pentheroudakis, G

ESMO Open 2019
Participants
Participates
Normal reaction
Functional status

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

Status
Disease
Name Identifier Synonyms
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
Authored
Reviewed
Created
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