Target General Information
Target ID	T56418
Target Name	ALK tyrosine kinase receptor (ALK)
Gene Name	ALK
Species	Homo sapiens
UniProt ID	ALK_HUMAN
Sequence	MGAIGLLWLLPLLLSTAAVGSGMGTGQRAGSPAAGPPLQPREPLSYSRLQRKSLAVDFVV PSLFRVYARDLLLPPSSSELKAGRPEARGSLALDCAPLLRLLGPAPGVSWTAGSPAPAEA RTLSRVLKGGSVRKLRRAKQLVLELGEEAILEGCVGPPGEAAVGLLQFNLSELFSWWIRQ GEGRLRIRLMPEKKASEVGREGRLSAAIRASQPRLLFQIFGTGHSSLESPTNMPSPSPDY FTWNLTWIMKDSFPFLSHRSRYGLECSFDFPCELEYSPPLHDLRNQSWSWRRIPSEEASQ MDLLDGPGAERSKEMPRGSFLLLNTSADSKHTILSPWMRSSSEHCTLAVSVHRHLQPSGR YIAQLLPHNEAAREILLMPTPGKHGWTVLQGRIGRPDNPFRVALEYISSGNRSLSAVDFF ALKNCSEGTSPGSKMALQSSFTCWNGTVLQLGQACDFHQDCAQGEDESQMCRKLPVGFYC NFEDGFCGWTQGTLSPHTPQWQVRTLKDARFQDHQDHALLLSTTDVPASESATVTSATFP APIKSSPCELRMSWLIRGVLRGNVSLVLVENKTGKEQGRMVWHVAAYEGLSLWQWMVLPL LDVSDRFWLQMVAWWGQGSRAIVAFDNISISLDCYLTISGEDKILQNTAPKSRNLFERNP NKELKPGENSPRQTPIFDPTVHWLFTTCGASGPHGPTQAQCNNAYQNSNLSVEVGSEGPL KGIQIWKVPATDTYSISGYGAAGGKGGKNTMMRSHGVSVLGIFNLEKDDMLYILVGQQGE DACPSTNQLIQKVCIGENNVIEEEIRVNRSVHEWAGGGGGGGGATYVFKMKDGVPVPLII AAGGGGRAYGAKTDTFHPERLENNSSVLGLNGNSGAAGGGGGWNDNTSLLWAGKSLQEGA TGGHSCPQAMKKWGWETRGGFGGGGGGCSSGGGGGGYIGGNAASNNDPEMDGEDGVSFIS PLGILYTPALKVMEGHGEVNIKHYLNCSHCEVDECHMDPESHKVICFCDHGTVLAEDGVS CIVSPTPEPHLPLSLILSVVTSALVAALVLAFSGIMIVYRRKHQELQAMQMELQSPEYKL SKLRTSTIMTDYNPNYCFAGKTSSISDLKEVPRKNITLIRGLGHGAFGEVYEGQVSGMPN DPSPLQVAVKTLPEVCSEQDELDFLMEALIISKFNHQNIVRCIGVSLQSLPRFILLELMA GGDLKSFLRETRPRPSQPSSLAMLDLLHVARDIACGCQYLEENHFIHRDIAARNCLLTCP GPGRVAKIGDFGMARDIYRASYYRKGGCAMLPVKWMPPEAFMEGIFTSKTDTWSFGVLLW EIFSLGYMPYPSKSNQEVLEFVTSGGRMDPPKNCPGPVYRIMTQCWQHQPEDRPNFAIIL ERIEYCTQDPDVINTALPIEYGPLVEEEEKVPVRPKDPEGVPPLLVSQQAKREEERSPAA PPPLPTTSSGKAAKKPTAAEISVRVPRGPAVEGGHVNMAFSQSNPPSELHKVHGSRNKPT SLWNPTYGSWFTEKPTKKNNPIAKKEPHDRGNLGLEGSCTVPPNVATGRLPGASLLLEPS SLTANMKEVPLFRLRHFPCGNVNYGYQQQGLPLEAATAPGAGHYEDTILKSKNSMNQPGP [Homo sapiens]
Drug and Corresponding Resistance Mutations
Mutation Info	Missense: C1156Y
Drugs	Drug Name Crizotinib Drug Info [4] Targeted Disease Lung Cancer Mutation Prevalence 1 out of 3 patients
Mutation Info	Missense: F1174C
Drugs	Drug Name Ceritinib Drug Info [7] Targeted Disease Non-small Cell Lung Cancer Mutation Prevalence 5 out of 11 patients
Mutation Info	Missense: F1174L
Drugs	Drug Name Crizotinib Drug Info [3] Targeted Disease Lung Cancer Mutation Prevalence 2 out of 11 patients
Mutation Info	Missense: F1174V
Drugs	Drug Name Crizotinib Drug Info [5] Targeted Disease Lung Cancer Mutation Prevalence 23-60% of the tumor purity patients
	Drug Name Ceritinib Drug Info [7] Targeted Disease Non-small Cell Lung Cancer
Mutation Info	Missense: G1123S
Drugs	Drug Name Ceritinib Drug Info [8] Targeted Disease Non-small Cell Lung Cancer
Mutation Info	Missense: G1202R
Drugs	Drug Name Crizotinib Drug Info [1], [2], [5] Targeted Disease Lung Cancer Mutation Prevalence 7 out of 29 patients
	Drug Name Ceritinib Drug Info [7] Targeted Disease Non-small Cell Lung Cancer Mutation Prevalence 3 out of 80 patients
	Drug Name Alectinib Drug Info [11] Mutation Prevalence 2 out of 9 patients
Mutation Info	Missense: G1269A
Drugs	Drug Name Crizotinib Drug Info [4] Targeted Disease Lung Cancer Mutation Prevalence 1 out of 3 patients
	Drug Name Ceritinib Drug Info [7] Targeted Disease Non-small Cell Lung Cancer
Mutation Info	Missense: I1171N
Drugs	Drug Name Alectinib Drug Info [9], [6]
Mutation Info	Missense: I1171S
Drugs	Drug Name Alectinib Drug Info [9], [10]
Mutation Info	Missense: I1171T
Drugs	Drug Name Crizotinib Drug Info [1], [2], [6] Targeted Disease Lung Cancer
	Drug Name Alectinib Drug Info [2]
Mutation Info	Missense: L1152R
Drugs	Drug Name Crizotinib Drug Info [1], [2] Targeted Disease Lung Cancer
Mutation Info	Missense: L1196M
Drugs	Drug Name Crizotinib Drug Info [1], [2] Targeted Disease Lung Cancer Mutation Prevalence 4 out of 18 patients
	Drug Name Ceritinib Drug Info [7] Targeted Disease Non-small Cell Lung Cancer
Mutation Info	Missense: S1206Y
Drugs	Drug Name Crizotinib Drug Info [1], [2], [7] Targeted Disease Lung Cancer Mutation Prevalence 4 out of 18 patients
Mutation Info	Missense: V1180L
Drugs	Drug Name Alectinib Drug Info [2]
References
REF 1	Mechanisms of acquired crizotinib resistance in ALK-rearranged lung Cancers. Sci Transl Med. 2012 Feb 8;4(120):120ra17.
REF 2	Two novel ALK mutations mediate acquired resistance to the next-generation ALK inhibitor alectinib. Clin Cancer Res. 2014 Nov 15;20(22):5686-96.
REF 3	Activating ESR1 mutations in hormone-resistant metastatic breast cancer. Nat Genet. 2013 Dec;45(12):1446-51.
REF 4	Genomic Aberrations in Crizotinib Resistant Lung Adenocarcinoma Samples Identified by Transcriptome Sequencing. PLoS One. 2016 Apr 5;11(4):e0153065.
REF 5	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. J Thorac Oncol. 2014 Apr;9(4):549-53.
REF 6	Secondary mutations at I1171 in the ALK gene confer resistance to both Crizotinib and Alectinib. J Thorac Oncol. 2014 Dec;9(12):e86-7.
REF 7	The ALK inhibitor ceritinib overcomes crizotinib resistance in non-small cell lung cancer. Cancer Discov. 2014 Jun;4(6):662-673.
REF 8	Identification of a Novel ALK G1123S Mutation in a Patient with ALK-rearranged Non-small-cell Lung Cancer Exhibiting Resistance to Ceritinib. J Thorac Oncol. 2015 Jul;10(7):e55-7.
REF 9	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. J Thorac Oncol. 2014 Dec;9(12):1821-5.
REF 10	ALK F1174V mutation confers sensitivity while ALK I1171 mutation confers resistance to alectinib. The importance of serial biopsy post progression. Lung Cancer. 2016 Jan;91:70-2.
REF 11	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. Clin Lung Cancer. 2016 Sep;17(5):e77-e94.

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