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《The Role of a Novel G796A Mutation in Exon 20 of EGFR》由会员上传分享，免费在线阅读，更多相关内容在行业资料-天天文库。
1、ANTICANCERRESEARCH27:2297-2304(2007)ANewMechanismforPrimaryResistancetoGefitinibinLungAdenocarcinoma:TheRoleofaNovelG796AMutationinExon20ofEGFRHIDETAKAURAMOTO1,TAKESHIUCHIUMI2,HIROTOIZUMI2,KIMITOSHIKOHNO2,TSUNEHIROOYAMA3,KENJISUGIO1andKOSEIYASUMOTO11SecondDepartmentofSurgery,2Depart
2、mentofMolecularBiologyand3DepartmentofEnvironmentalHealth,SchoolofMedicine,UniversityofOccupationalandEnvironmentalHealth,Kitakyushu807-8555,JapanAbstract.Subsetsofnon-smallcelllungcancer(NSCLC)chemotherapeuticagents(1,2).Theresponseratesare10patientswhocarryactivatingsomaticmutatio
3、nsoftheto20percentwhentyrosinekinaseinhibitors(TKI)suchasepidermalgrowthfactorreceptor(EGFR)havedemonstratedgefitiniborerlotonibareusedassecond-orthird-lineanincreasedprobabilityofobtainingobjectiveresponsestothetreatmentsforadvanceddisease(3-5).Althoughsuchreceptortyrosinekinaseinh
4、ibitors(TKIs),gefitinibandfactorsasfemalesex,adenocarcinoma,andnohistoryoferlotinib.However,asubstantialproportionofthecaseswithsmokingareallconsideredtobeprobablemarkersforasomaticmutations,whichsuggestsensitivitytogefitinib,arefavorableresponsetoTKI(6),activatingepidermalgrowthpri
5、maryresistanttoit.Aprimaryresistantcaseoflungfactorreceptor(EGFR)mutationshavealsobeenreportedadenocarcinomathatwasfoundtocarrybothdelE746-A750tobehighlysignificantpredictorsoftheresponse(7-16).andaG796AmutationintheEGFRisreported.Invitro,aAlthoughpatientswithactivatingEGFRmutations
6、maybestablecloneofcellsbearingtheG796Amutationwasexpectedtorespondtogefitinib,aproportionofthemapproximately50,000-foldlesssensitivetogefitinibinactuallydonotobtainanobjectiveresponse.ThemolecularcomparisontocellscarryingthedelE746-A750mutantEGFR.mechanismofsuchprimaryresistancerema
7、insunresolved.ThisstudysuggeststhatscreeningtumoursamplesforarangeThisisthefirstdescriptionofprimaryresistancetoofEGFRmutationsmayimproveourabilitytoidentifythegefitinibassociatedwithmutationsofbothG796A(apatientsmostlikelytobenefitfromEFGRTKIs.substitutionofalanineforglycineatposit
8、ion796)anddelE746-A
