BRAF in Melanoma Pathogenesis, Diagnosis, Inhibition, and Resistance英文文献资料.docVIP

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BRAF in Melanoma Pathogenesis, Diagnosis, Inhibition, and Resistance英文文献资料.doc

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BRAF in Melanoma Pathogenesis, Diagnosis, Inhibition, and Resistance英文文献资料

HindawiPublishingCorporation JournalofSkinCancer Volume2011,ArticleID423239,8pages doi:10.1155/2011/423239 ReviewArticle BRAFinMelanoma:Pathogenesis,Diagnosis,Inhibition, andResistance RyanJ.Sullivan andKeithT.Flaherty 1 2 1 2 DivisionofHematology/Oncology,BethIsraelDeaconessMedicalCenter,HarvardMedicalSchool,Boston,MA02114,USA MassachusettsGeneralHospitalCancerCenter,HarvardMedicalSchool,Boston,MA02114,USA CorrespondenceshouldbeaddressedtoKeithT.Flaherty,k?aherty@ Received10July2011;Revised27September2011;Accepted28September2011 AcademicEditor:S.Ugurel Copyright?2011R.J.SullivanandK.T.Flaherty. This is an open access article distributed under the Creative Commons AttributionLicense,whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalworkis properlycited. SincetheinitialdiscoverythatasubsetofpatientswithcutaneousmelanomaharborBRAFmutations,substantialresearchhas beenfocusedondeterminingthepathologicconsequencesofBRAFmutations,optimizingdiagnostictechniquestoidentifythese mutations,anddevelopingtherapeuticinterventionstoinhibitthefunctionofthistargetinmutation-bearingtumors.Recently, advanceshavebeenmadewhicharerevolutionizingthestandardofcareforpatientswithBRAFmutantmelanoma.Thispaper providesanoverviewonthepathogenicrami?cationsofmutantBRAFsignaling,thelatestmoleculartestingmethodstodetect BRAFmutations,andthemostrecentclinicaldataofBRAFpathwayinhibitorsinpatientswithmelanomaandBRAFmutations. Finally,emergingmechanismsofresistancetoBRAFinhibitorsandwaysofovercomingthisresistancearediscussed. 1.Introduction activationofextracellularsignal-regulatedkinase(ERK)leads tothepromotionofcellulargrowthandoppositionofapop- tosis and, ultimately, transformation into melanoma [5]. Thisenhancedsignaling,however,alsorendersmutatedcells susceptible to the use of small molecule inhibitors which targetvariousBRAFpathwaymediators[5–7]. Melanomaiscurrentlythe5thand7thmostcommoncancer inAmericanmenandwomen,respectively[1].