Resistance mutation info of target

Target General Information
Target ID T56418
Target Name ALK tyrosine kinase receptor (ALK) Target Info
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 Resistance Mutation and Corresponding Drugs
Mutation Info Missense: C1156Y
Drugs
Drug Name Crizotinib Drug Info [1]
Targeted Disease Lung Cancer
Mutation Prevalence 1 out of 3 patients
Mutation Info Missense: F1174C
Drugs
Drug Name Ceritinib Drug Info [2]
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 [4]
Targeted Disease Lung Cancer
Mutation Prevalence 23-60% of the tumor purity patients
Drug Name Ceritinib Drug Info [2]
Targeted Disease Non-small Cell Lung Cancer
Mutation Info Missense: G1123S
Drugs
Drug Name Ceritinib Drug Info [5]
Targeted Disease Non-small Cell Lung Cancer
Mutation Info Missense: G1202R
Drugs
Drug Name Crizotinib Drug Info [6], [4], [7]
Targeted Disease Lung Cancer
Mutation Prevalence 7 out of 29 patients
Drug Name Ceritinib Drug Info [2]
Targeted Disease Non-small Cell Lung Cancer
Mutation Prevalence 3 out of 80 patients
Drug Name Alectinib Drug Info [8]
Targeted Disease Lung Cancer
Mutation Prevalence 2 out of 9 patients
Mutation Info Missense: G1269A
Drugs
Drug Name Crizotinib Drug Info [1]
Targeted Disease Lung Cancer
Mutation Prevalence 1 out of 3 patients
Drug Name Ceritinib Drug Info [2]
Targeted Disease Non-small Cell Lung Cancer
Mutation Info Missense: I1171N
Drugs
Drug Name Alectinib Drug Info [9], [10]
Targeted Disease Lung Cancer
Mutation Info Missense: I1171S
Drugs
Drug Name Alectinib Drug Info [9], [11]
Targeted Disease Lung Cancer
Mutation Info Missense: I1171T
Drugs
Drug Name Crizotinib Drug Info [6], [7], [10]
Targeted Disease Lung Cancer
Drug Name Alectinib Drug Info [7]
Targeted Disease Lung Cancer
Mutation Info Missense: L1152R
Drugs
Drug Name Crizotinib Drug Info [6], [7]
Targeted Disease Lung Cancer
Mutation Info Missense: L1196M
Drugs
Drug Name Crizotinib Drug Info [6], [7]
Targeted Disease Lung Cancer
Mutation Prevalence 4 out of 18 patients
Drug Name Ceritinib Drug Info [2]
Targeted Disease Non-small Cell Lung Cancer
Mutation Info Missense: S1206Y
Drugs
Drug Name Crizotinib Drug Info [6], [2], [7]
Targeted Disease Lung Cancer
Mutation Prevalence 4 out of 18 patients
Mutation Info Missense: V1180L
Drugs
Drug Name Alectinib Drug Info [7]
Targeted Disease Lung Cancer
Reference
REF 1Genomic Aberrations in Crizotinib Resistant Lung Adenocarcinoma Samples Identified by Transcriptome Sequencing. PLoS One. 2016 Apr 5;11(4):e0153065. doi: 10.1371/journal.pone.0153065. eCollection 2016.
REF 2The ALK inhibitor ceritinib overcomes crizotinib resistance in non-small cell lung cancer. Cancer Discov. 2014 Jun;4(6):662-673. doi: 10.1158/2159-8290.CD-13-0846. Epub 2014 Mar 27.
REF 3Activating ESR1 mutations in hormone-resistant metastatic breast cancer. Nat Genet. 2013 Dec;45(12):1446-51. doi: 10.1038/ng.2823. Epub 2013 Nov 3.
REF 4Next-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. doi: 10.1097/JTO.0000000000000094.
REF 5Identification 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. doi: 10.1097/JTO.0000000000000509.
REF 6Mechanisms of acquired crizotinib resistance in ALK-rearranged lung Cancers. Sci Transl Med. 2012 Feb 8;4(120):120ra17. doi: 10.1126/scitranslmed.3003316. Epub 2012 Jan 25.
REF 7Two novel ALK mutations mediate acquired resistance to the next-generation ALK inhibitor alectinib. Clin Cancer Res. 2014 Nov 15;20(22):5686-96. doi: 10.1158/1078-0432.CCR-14-1511. Epub 2014 Sep 16.
REF 8Anaplastic 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. doi: 10.1016/j.cllc.2016.03.005. Epub 2016 Mar 30.
REF 9Identification 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. doi: 10.1097/JTO.0000000000000368.
REF 10Secondary mutations at I1171 in the ALK gene confer resistance to both Crizotinib and Alectinib. J Thorac Oncol. 2014 Dec;9(12):e86-7. doi: 10.1097/JTO.0000000000000358.
REF 11ALK 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. doi: 10.1016/j.lungcan.2015.09.006. Epub 2015 Sep 12.

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