Resistance mutation info of target

Target General Information
Target ID T59328
Target Name Epidermal growth factor receptor (EGFR) Target Info
Gene Name EGFR
Species Homo sapiens
Uniprot ID EGFR_HUMAN
Sequence MRPSGTAGAALLALLAALCPASRALEEKKVCQGTSNKLTQLGTFEDHFLSLQRMFNNCEV
VLGNLEITYVQRNYDLSFLKTIQEVAGYVLIALNTVERIPLENLQIIRGNMYYENSYALA
VLSNYDANKTGLKELPMRNLQEILHGAVRFSNNPALCNVESIQWRDIVSSDFLSNMSMDF
QNHLGSCQKCDPSCPNGSCWGAGEENCQKLTKIICAQQCSGRCRGKSPSDCCHNQCAAGC
TGPRESDCLVCRKFRDEATCKDTCPPLMLYNPTTYQMDVNPEGKYSFGATCVKKCPRNYV
VTDHGSCVRACGADSYEMEEDGVRKCKKCEGPCRKVCNGIGIGEFKDSLSINATNIKHFK
NCTSISGDLHILPVAFRGDSFTHTPPLDPQELDILKTVKEITGFLLIQAWPENRTDLHAF
ENLEIIRGRTKQHGQFSLAVVSLNITSLGLRSLKEISDGDVIISGNKNLCYANTINWKKL
FGTSGQKTKIISNRGENSCKATGQVCHALCSPEGCWGPEPRDCVSCRNVSRGRECVDKCN
LLEGEPREFVENSECIQCHPECLPQAMNITCTGRGPDNCIQCAHYIDGPHCVKTCPAGVM
GENNTLVWKYADAGHVCHLCHPNCTYGCTGPGLEGCPTNGPKIPSIATGMVGALLLLLVV
ALGIGLFMRRRHIVRKRTLRRLLQERELVEPLTPSGEAPNQALLRILKETEFKKIKVLGS
GAFGTVYKGLWIPEGEKVKIPVAIKELREATSPKANKEILDEAYVMASVDNPHVCRLLGI
CLTSTVQLITQLMPFGCLLDYVREHKDNIGSQYLLNWCVQIAKGMNYLEDRRLVHRDLAA
RNVLVKTPQHVKITDFGLAKLLGAEEKEYHAEGGKVPIKWMALESILHRIYTHQSDVWSY
GVTVWELMTFGSKPYDGIPASEISSILEKGERLPQPPICTIDVYMIMVKCWMIDADSRPK
FRELIIEFSKMARDPQRYLVIQGDERMHLPSPTDSNFYRALMDEEDMDDVVDADEYLIPQ
QGFFSSPSTSRTPLLSSLSATSNNSTVACIDRNGLQSCPIKEDSFLQRYSSDPTGALTED
SIDDTFLPVPEYINQSVPKRPAGSVQNPVYHNQPLNPAPSRDPHYQDPHSTAVGNPEYLN
TVQPTCVNSTFDSPAHWAQKGSHQISLDNPDYQQDFFPKEAKPNGIFKGSTAENAEYLRV
APQSSEFIGA [Homo sapiens]
Drug Resistance Mutation and Corresponding Drugs
Mutation Info Missense: C797S
Drugs
Drug Name Azd9291 Drug Info [1]
Targeted Disease Non-small Cell Lung Cancer
Mutation Prevalence 6 out of 15 patients
Drug Name Hm61713 Drug Info [2]
Targeted Disease Lung Cancer
Mutation Info Missense: D761Y
Drugs
Drug Name Gefitinib Drug Info [3], [4]
Targeted Disease Non-small Cell Lung Cancer
Drug Name Erlotinib Drug Info [4]
Targeted Disease Lung Cancer
Mutation Info Missense: G465R
Drugs
Drug Name Cetuximab Drug Info [5], [6], [7], [8]
Targeted Disease Colorectal cancer
Drug Name Panitumumab Drug Info [7]
Targeted Disease Colorectal cancer
Mutation Info Missense: I491M
Drugs
Drug Name Cetuximab Drug Info [6]
Targeted Disease Colorectal cancer
Mutation Info Missense: K467T
Drugs
Drug Name Cetuximab Drug Info [5], [6], [7], [8]
Targeted Disease Colorectal cancer
Mutation Info Missense: L798I
Drugs
Drug Name Rociletinib Drug Info [9]
Targeted Disease Lung Cancer
Mutation Info Missense: L858R
Drugs
Drug Name Gefitinib Drug Info [10]
Targeted Disease Non-small Cell Lung Cancer
Mutation Info Missense: R451C
Drugs
Drug Name Cetuximab Drug Info [5], [6], [7], [8]
Targeted Disease Colorectal cancer
Mutation Info Missense: S464L
Drugs
Drug Name Cetuximab Drug Info [6]
Targeted Disease Colorectal cancer
Mutation Info Missense: S492R
Drugs
Drug Name Cetuximab Drug Info [5]
Targeted Disease Colorectal cancer
Mutation Prevalence 2 out of 10 patients
Mutation Info Missense: T790M
Drugs
Drug Name Gefitinib Drug Info [11]
Targeted Disease Non-small Cell Lung Cancer
Mutation Prevalence 92 out of 103 patients in all EGFR mutations
Drug Name Afatinib Drug Info [12]
Targeted Disease Lung Cancer
Mutation Prevalence 8 out of 141 patients
Drug Name Erlotinib Drug Info [13], [14]
Targeted Disease Lung Cancer
Mutation Prevalence 50% of the patients
Drug Name Azd9291 Drug Info [1], [15]
Targeted Disease Non-small Cell Lung Cancer
Mutation Prevalence 4 out of 15 patients
Drug Name Co-1686 Drug Info [16]
Targeted Disease Non-small Cell Lung Cancer
Drug Name Xl647 Drug Info [17]
Targeted Disease Non-small Cell Lung Cancer
Drug Name Type I TKIs Drug Info [18], [19], [20], [21]
Targeted Disease Non-small Cell Lung Cancer
Reference
REF 1Acquired EGFR C797S mutation mediates resistance to AZD9291 in non-small cell lung cancer harboring EGFR T790M. Nat Med. 2015 Jun;21(6):560-2. doi: 10.1038/nm.3854. Epub 2015 May 4.
REF 2Acquired C797S Mutation upon Treatment with a T790M-Specific Third-Generation EGFR Inhibitor (HM61713) in Non-Small Cell Lung Cancer. J Thorac Oncol. 2016 Apr;11(4):e45-7. doi: 10.1016/j.jtho.2015.12.093. Epub 2015 Dec 31.
REF 3Novel D761Y and common secondary T790M mutations in epidermal growth factor receptor-mutant lung adenocarcinomas with acquired resistance to kinase inhibitors. Clin Cancer Res. 2006 Nov 1;12(21):6494-501.
REF 4Activating and resistance mutations of EGFR in non-small-cell lung cancer: role in clinical response to EGFR tyrosine kinase inhibitors. Oncogene. 2009 Aug;28 Suppl 1:S24-31. doi: 10.1038/onc.2009.198.
REF 5Identification of a mutation in the extracellular domain of the Epidermal Growth Factor Receptor conferring cetuximab resistance in colorectal cancer. Nat Med. 2012 Jan 22;18(2):221-3. doi: 10.1038/nm.2609.
REF 6Emergence of Multiple EGFR Extracellular Mutations during Cetuximab Treatment in Colorectal Cancer. Clin Cancer Res. 2015 May 1;21(9):2157-66. doi: 10.1158/1078-0432.CCR-14-2821. Epub 2015 Jan 26.
REF 7Epidermal growth factor receptor mutation mediates cross-resistance to panitumumab and cetuximab in gastrointestinal cancer. Oncotarget. 2015 May 20;6(14):12035-47.
REF 8The First-in-class Anti-EGFR Antibody Mixture Sym004 Overcomes Cetuximab Resistance Mediated by EGFR Extracellular Domain Mutations in Colorectal Cancer. Clin Cancer Res. 2016 Jul 1;22(13):3260-7. doi: 10.1158/1078-0432.CCR-15-2400. Epub 2016 Feb 17.
REF 9Circulating tumour DNA profiling reveals heterogeneity of EGFR inhibitor resistance mechanisms in lung cancer patients. Nat Commun. 2016 Jun 10;7:11815. doi: 10.1038/ncomms11815.
REF 10Histological transformation from non-small cell to small cell lung carcinoma after treatment with epidermal growth factor receptor-tyrosine kinase inhibitor. Thorac Cancer. 2015 Nov;6(6):800-4. doi: 10.1111/1759-7714.12217. Epub 2014 Dec 29.
REF 11Analysis of epidermal growth factor receptor gene mutation in patients with non-small cell lung cancer and acquired resistance to gefitinib. Clin Cancer Res. 2006 Oct 1;12(19):5764-9.
REF 12Afatinib versus placebo for patients with advanced, metastatic non-small-cell lung cancer after failure of erlotinib, gefitinib, or both, and one or two lines of chemotherapy (LUX-Lung 1): a phase 2b/3 randomised trial. Lancet Oncol. 2012 May;13(5):528-38. doi: 10.1016/S1470-2045(12)70087-6. Epub 2012 Mar 26.
REF 13Acquired resistance to BRAF inhibitors mediated by a RAF kinase switch in melanoma can be overcome by cotargeting MEK and IGF-1R/PI3K. Cancer Cell. 2010 Dec 14;18(6):683-95. doi: 10.1016/j.ccr.2010.11.023.
REF 14Combinations of BRAF, MEK, and PI3K/mTOR inhibitors overcome acquired resistance to the BRAF inhibitor GSK2118436 dabrafenib, mediated by NRAS or MEK mutations. Mol Cancer Ther. 2012 Apr;11(4):909-20. doi: 10.1158/1535-7163.MCT-11-0989. Epub 2012 Mar 2.
REF 15Mechanisms of Acquired Resistance to AZD9291: A Mutation-Selective, Irreversible EGFR Inhibitor. J Thorac Oncol. 2015 Dec;10(12):1736-44. doi: 10.1097/JTO.0000000000000688.
REF 16Discovery of a mutant-selective covalent inhibitor of EGFR that overcomes T790M-mediated resistance in NSCLC. Cancer Discov. 2013 Dec;3(12):1404-15.
REF 17Phase II study of the multitargeted tyrosine kinase inhibitor XL647 in patients with non-small-cell lung cancer. J Thorac Oncol. 2012 May;7(5):856-65. doi: 10.1097/JTO.0b013e31824c943f.
REF 18Acquired resistance to EGFR tyrosine kinase inhibitors in EGFR-mutant lung cancer: distinct natural history of patients with tumors harboring the T790M mutation. Clin Cancer Res. 2011 Mar 15;17(6):1616-22. doi: 10.1158/1078-0432.CCR-10-2692. Epub 2010 Dec 6.
REF 19A noninvasive system for monitoring resistance to epidermal growth factor receptor tyrosine kinase inhibitors with plasma DNA. J Thorac Oncol. 2011 Oct;6(10):1639-48. doi: 10.1097/JTO.0b013e31822956e8.
REF 20Lung cancers with acquired resistance to EGFR inhibitors occasionally harbor BRAF gene mutations but lack mutations in KRAS, NRAS, or MEK1. Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):E2127-33. doi: 10.1073/pnas.1203530109. Epub 2012 Jul 6.
REF 21Rebiopsy of non-small cell lung cancer patients with acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitor: Comparison between T790M mutation-positive and mutation-negative populations. Cancer. 2013 Dec 15;119(24):4325-32. doi: 10.1002/cncr.28364. Epub 2013 Sep 16.

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