非小细胞肺癌的放射和吉非替尼综合治疗.ppt

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1、第2届广州国际肺癌论坛2011年8月20日,广州蒋国梁复旦大学附属肿瘤医院非小细胞肺癌的放射和吉非替尼综合治疗Outcomeofnon-smallcellcarcinomaStageandtmt5-yrsurvivalI-IIsurgery48-70%I-IIinoperable,SBRT～40%IIIa(surgery±otherTmt)15-27%IIIa(RT＋Chemo)14-20%IIIb(RT＋Chemo)5-7%进一步提高非小细胞肺癌的疗效：放疗＋靶向药物治疗Gefitinibenhancedradiosen

2、sitivityoftumorcellsSurvivalcurveofOralSCC(invitro)ShintaniS.IntJCancer2003;107:1030–37Shoulderofsurvivalcurvedisappear(inhibitionforSLDrepair)Slopofsurvivalcurvereduced(intrinsicradiosensitivityincreased)GefitinibenhancedradiosensitivityoftumorcellsGEO(rectalcarc

3、inoma)invivo(tumorre-growthdelay)10Gy/fx×4fx+Iressa2.5mgipd1-5×4wksBiancoetal.ClinCancerRes2002;8:3250-3258Iressa+RTControlRTIressaThepercentageofSphasedecreasedafterIressaIressa+RT(GEOinvivo)BiancoC.ClinCancerRes2002;8:3250-3258MechanismofGefitinibradiosensitizat

4、ionGefitinibspeedsupapoptosisoftumorcellsafterRTGEOinvivoBiancoC.ClinCancerRes2002;8:3250-3258RT+IressaRTIressaGefitinibinhibitsRTinduceddamagerepairOralSCC(Westernblot)ShintaniS.etal.IntJCancer2003;107:1030–1037RTdamageDNANeedDNArepairenzymeRTenzymeDNArepairGe

5、fitinibenzymeDNArepairIressa+RTinOralSCC(Westernblot)RTcouldactivateEGFR-TKsignalingpathway(Ras-Raf-MAPK).Andinitiatesamultistepphosphorylationcascadethatleadstoactivationthepathway,andstimulatescell-cycleprogressionShintaniS.IntJCancer2003;107:1030–1037Gefitini

6、bcouldinhibitmultistepphosphorylationofEGFRsignalingpathway,soslowdownthetumorcellproliferationandenhancetheradiationsterilization.PossiblemechanismsforradiosensitizationofGefitinibDecreasepercentageofSphaseandincreaseG2/MphasesoftumorcellsEnhancetumorcellapoptosi

7、safterRTInhibitradiationinducedDNArepairInhibitmultistepphosphorylationofEGFRsignalingpathway,soreducethetumorcellproliferationafterRTIressa提高了肿瘤固有的放射敏感性，抑止了肿瘤放射损伤后的修复和增殖CombinationofradiationtherapyandGefitinibforstageIIIb/IVnon-smallcelllungcarcinomaClinicalphas

8、eItrialIrradiationdoseescalation(NCT00497250)Rationales:Gefitinibasradiosensitizertoenhancelocaltumorsterilization.Inhibitordelaythegrowthofmicrometasta