Target General Information
Target ID	T59328
Target Name	Epidermal growth factor receptor (EGFR)
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 and Corresponding Resistance Mutations
Mutation Info	Missense: C797S
Drugs	Drug Name Hm61713 Drug Info [13] Targeted Disease Lung Cancer
	Drug Name Azd9291 Drug Info [19] Mutation Prevalence 6 out of 15 patients
Mutation Info	Missense: D761Y
Drugs	Drug Name Gefitinib Drug Info [8], [9] Targeted Disease Breast Cancer; Non-small Cell Lung Cancer
	Drug Name Erlotinib Drug Info [9] Targeted Disease Lung Cancer
Mutation Info	Missense: G465R
Drugs	Drug Name Panitumumab Drug Info [2] Targeted Disease Colorectal cancer
	Drug Name Cetuximab Drug Info [2], [3], [4], [5] Targeted Disease Colorectal cancer
Mutation Info	Missense: I491M
Drugs	Drug Name Cetuximab Drug Info [4] Targeted Disease Colorectal cancer
Mutation Info	Missense: K467T
Drugs	Drug Name Cetuximab Drug Info [2], [3], [4], [5] Targeted Disease Colorectal cancer
Mutation Info	Missense: L798I
Drugs	Drug Name Rociletinib Drug Info [21]
Mutation Info	Missense: L858R
Drugs	Drug Name Gefitinib Drug Info [10] Targeted Disease Breast Cancer; Non-small Cell Lung Cancer
Mutation Info	Missense: R451C
Drugs	Drug Name Cetuximab Drug Info [2], [3], [4], [5] Targeted Disease Colorectal cancer
Mutation Info	Missense: S464L
Drugs	Drug Name Cetuximab Drug Info [4] Targeted Disease Colorectal cancer
Mutation Info	Missense: S492R
Drugs	Drug Name Cetuximab Drug Info [3] Targeted Disease Colorectal cancer Mutation Prevalence 2 out of 10 patients
Mutation Info	Missense: T790M
Drugs	Drug Name Xl647 Drug Info [1] Targeted Disease Non-small Cell Lung Cancer
	Drug Name Afatinib Drug Info [6] Targeted Disease Lung Cancer Mutation Prevalence 8 out of 141 patients
	Drug Name Gefitinib Drug Info [7] Targeted Disease Breast Cancer; Non-small Cell Lung Cancer Mutation Prevalence 92 out of 103 patients in all EGFR mutations
	Drug Name Erlotinib Drug Info [11], [12] Targeted Disease Lung Cancer Mutation Prevalence 50% of the patients
	Drug Name Co-1686 Drug Info [14] Targeted Disease Non-small Cell Lung Cancer
	Drug Name Type I TKIs Drug Info [15], [16], [17], [18]
	Drug Name Azd9291 Drug Info [19], [20] Mutation Prevalence 4 out of 15 patients
References
REF 1	Phase 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.
REF 2	Epidermal growth factor receptor mutation mediates cross-resistance to panitumumab and cetuximab in gastrointestinal cancer. Oncotarget. 2015 May 20;6(14):12035-47.
REF 3	Identification 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.
REF 4	Emergence of Multiple EGFR Extracellular Mutations during Cetuximab Treatment in Colorectal Cancer. Clin Cancer Res. 2015 May 1;21(9):2157-66.
REF 5	The 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.
REF 6	Afatinib 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.
REF 7	Analysis 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 8	Novel 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 9	Activating 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.
REF 10	Histological 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.
REF 11	Combinations 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.
REF 12	Acquired 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.
REF 13	Acquired 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.
REF 14	Discovery of a mutant-selective covalent inhibitor of EGFR that overcomes T790M-mediated resistance in NSCLC. Cancer Discov. 2013 Dec;3(12):1404-15.
REF 15	Acquired 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.
REF 16	A 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.
REF 17	Lung 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.
REF 18	Rebiopsy 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.
REF 19	Acquired EGFR C797S mutation mediates resistance to AZD9291 in non-small cell lung cancer harboring EGFR T790M. Nat Med. 2015 Jun;21(6):560-2.
REF 20	Mechanisms of Acquired Resistance to AZD9291: A Mutation-Selective, Irreversible EGFR Inhibitor. J Thorac Oncol. 2015 Dec;10(12):1736-44.
REF 21	Circulating tumour DNA profiling reveals heterogeneity of EGFR inhibitor resistance mechanisms in lung cancer patients. Nat Commun. 2016 Jun 10;7:11815.

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