BRAF基因突变在甲状腺乳头状癌中的应用.ppt

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1、李永平DoctorLiBRAF基因突变在甲状腺乳头状癌中的临床应用2014-04-23*目录CONTENTS相关文献回顾BRAF基因BRAF与PTC文献精选展望*相关文献回顾1*BRAF文献回顾BRAFMutationsinHairy-CellLeukemiaTheBRAFV600EmutationwaspresentinallpatientswithHCLwhowereevaluatedImplicationsforthepathogenesis,diagnosis,andtargetedthera

2、pyNEnglJMedJune162011;364:2305-15.；毛细胞白血病所有毛细胞白血病BRAFV600E发生了变异可以用来研究发病机理、诊断、靶向治疗*BRAF文献回顾CetuximabandChemotherapyasInitialTreatmentforMetastaticColorectalCancerCetuximabplusFOLFIRIcomparedwithFOLFIRIalonereducedtheriskofprogressionofmetastaticcolorecta

3、lcancerNEnglJMedapril2,2009;360:1408-17.转移性结直肠癌西妥昔单抗合并FOLFIRI降低对KRAS突变转移性结直肠癌患者的疾病进展风险2011版NCCN提出：具有BRAF突变的患者预后差，一线治疗后疾病进展的，利用西妥昔单抗治疗是无效的*BRAF文献回顾ImprovedSurvivalWithVemurafenibInMelanomaWithBRAFV600EMutationAberrantactivationoftheBRAFkinaseoccursin60%o

4、fmelanomas,andalthoughBRAFinhibitorshaveshownsignificantearlyclinicalsuccessNEnglJMed2011;364:2507-16.黑色素瘤在黑色素瘤中有60%患者发生BRAFV600E突变发生BRAFV600E突变的患者经vemurafenib（威罗菲尼）治疗，患者的总生存率和无进展生存率分别提高（37%&26%）。但易产生耐药。*BRAF基因介绍2*PTC中BRAF基因突变的分布Theworldwideprevalenceof

5、BRAFmutationsinPTCEndocrine-RelatedCancer(2006)13455–464文献结论※B-RAFV600Emutationwasfoundin99outof260PTCs(38%)※TheB-RAFV600Emutationwaspresentin48.3%ofcasesofclassicPTC(85outof176),in17.6%(nineoutof51)offollicularvariantsofPTC,in21.7%(fiveoutof23)ofotherP

6、TCvariantsandinnoneofthetenpoorlydifferentiatedtumors.※TheB-RAFV600Ewascorrelatedwithanolderageatdiagnosis(P=0.01)Endocrine-RelatedCancer(2006)13455–464BRAF基因突变的致病机理Themodelillustratesthetwomajorsignalingpathways,thePI3K/AktandtheMAPkinasepathways。Thein

7、creasingcolorintensityofthecirclerepresentstheincreasingprogressionandaggressivenessofthetumor.MAPKpathway,theRas→Raf→MEK→MAP→ERKpathway.ClinCancerRes2007;13:1161-1170.PengHou,DingxieLiu,YuanShan,etal.BRAF信号通路ExpertRev.Mol.Diagn.©FutureScienceGroup(2012

8、)BRAF蛋白与KRAS蛋白同为RAS-RAF-MEK-ERK信号通路中上游调节因子，在MAPK/ERK信号通路中起着举足轻重的作用；通过这些途径，将胞外信号转化为胞内信号，从而有效应对外界的信号刺激，调节细胞的生长、增殖、分化，抑制细胞的凋亡。AdPRASBRAFMEKERKERKNucleusNucleargeneregulationFigure1.MolecularsignalingoftheMAPkinasepathway.RTKdimerize