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1、ActaMed.Okayama,2014Vol.68,No.4,pp.191ﾝ200CopyrightⒸ2014byOkayamaUniversityMedicalSchool.Reviewhttp://escholarship.lib.okayama-u.ac.jp/amo/DrugResistancetoEGFRTyrosineKinaseInhibitorsforNon-smallCellLungCancerKazuhikoShiena,b,HiromasaYamamotob,JunichiSohb,Shi
2、nichiroMiyoshib,andShinichiToyookaa,b＊abDepartmentsofClinicalGenomicMedicine,andGeneralThoracicSurgeryandBreastandEndocrinologicalSurgery,OkayamaUniversityGraduateSchoolofMedicine,DentistryandPharmaceuticalSciences,Okayama700-8558,JapanNon-smallcelllungcancer
3、(NSCLC)harboringanactivatingmutationwithintheepidermalgrowthfactorreceptor(EGFR)wasdefinedasaclinicallydistinctmoleculargroup.Theselesionsshowonco-geneaddictiontoEGFRanddramaticresponsestotheEGFRtyrosinekinaseinhibitors(TKIs).SeverallargePhaseIIItrialshaveshow
4、nthatEGFR-TKIsimprovedtheprogression-freesurvivalofpatientswithEGFRmutantNSCLCcomparedtoconventionalchemotherapy.However,thelong-termeffectivenessofEGFR-TKIsisusuallylimitedbecauseofacquireddrugresistance.ToovercomethisresistancetoEGFR-TKIs,itwillbeessentialto
5、identifythespecificmechanismsunderlyingtheresis-tance.Manyinvestigatorshaveattemptedtoidentifythemechanismsusingpreclinicalmodelsanddrug-resistantclinicalsamples.Asaresult,severalmechanismshavebeenshowedtoberesponsiblefortheresistance,butnotalloftherelevantmec
6、hanismshavebeenuncovered.Inthisreview,weprovideanoverviewofmechanismsunderlyingdrug-resistancetoEGFR-TKIs,focusingonresultsobtainedwithpreclinicalmodels,andwepresentsomepossiblestrategiestoovercometheEGFR-TKIresistance.Keywords:non-smallcelllungcancer,EGFRmut
7、ation,tyrosine-kinaseinhibitor,drugresistance,cancerstemcellLungcancercontinuestobetheleadingcauseofhasbeenuncoveredinregardtobothEGFRandotherdeathamongpatientswithmalignanttumorsgenesintheEGFRfamilyandtheirdownstreamworldwide[1].Manypatientsarediagnosedafter
8、thegenes.cancerhasalreadyspreadtodistantsitesordirectlyEGFR-TKIshaveexhibitedsignificantantiprolif-beyondtheprimarysite,resultinginaninoperableerativeeffectsagainstNSCLCwithEGFR-activatings
