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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