你所需,我所有_肿瘤液体活检方案有Thermo Fisher就够%

TheworldleaderinservingscienceProprietary&Confidential你所需，我所有——肿瘤液体活检方案有ThermoFisher就够了ForResearchUseOnly.Notforuseindiagnosticprocedures2©2016ThermoFisherScientificCorporation.Allrightsreserved.MoleculartestingguidelinesforinformingtreatmentoptionsforNSCLCpatients,asrecommendedbyCAP1,AMP1,IASLC1,andNCCN2:•EGFR,ALK,ROS1,BRAF,andPDL1testingforfirst-linetherapies2•Emergingtargetedagentsforpatientswithothergeneticalterations,includingKRAS,HER2,MET,andRET2•Broadermolecularprofilingtoidentifyraredrivermutationsforwhicheffectivedrugsmaybealreadyavailable,ortoappropriatelycounselpatientsregardingtheavailabilityofclinicaltrials;broadmolecularprofilingisakeycomponentoftheimprovementtocareofpatientswithNSCLC2多基因检测为相关指南所推荐精准治疗方案的制定离不开多基因检测，多种相关指南均建议实体肿瘤患者可尝试多基因检测。1.JournalofMolecularDiagnostics,MolecularTestingGuidelineforSelectionofLungCancerPatientsforEGFRandALKTyrosineKinaseInhibitors.GuidelinefromtheCollegeofAmericanPathologists,InternationalAssociationfortheStudyofLungCancer,andAssociationforMolecularPathology15(4),July2013.2.NCCNClinicalPracticeGuidelinesinOncology(NCCNGuidelines™),Non-SmallCellLungCancer,v8.2017,NCCN.org.Forinvitrodiagnosticuse.实时的肿瘤分子分型有助于选择最为合适的治疗策略Therapy1Therapy2Therapy3EGFRExon19EGFRExon19(20%)EGFRExon19(29%)EGFRExon19(20%)KRASp.G13D(55%)T790M(6%)T790M(2%)METp.N375S(40%)P53p.G245V(10%)P53p.G245V(3%)METp.T1010I(20%)METp.N375S(59%)METp.N375S(55%)BaselineTime1TBB/TTBTime2Pleuraerguss(90%)Time3Liquidbiopsy(ctDNA)EGFR(Exon19)•肿瘤分子分型的时空特异性•治疗压力可能会导致肿瘤发Th变异，产Th耐药突变或者驱动基因的改变3©2016ThermoFisherScientificCorporation.Allrightsreserved.ForResearchUseOnly.Notforuseindiagnosticprocedures液体活检可作为组织活检的有效补充液体活检•非侵入性的实时取样：为需要实时监控疗效的靶向治疗患者提供耐药监测的可能•取样容易：为无手术样本或难以穿刺的肿瘤患者提供精准靶向治疗方案的可能4©2016ThermoFisherScientificCorporation.Allrightsreserved.ForResearchUseOnly.NotforuseindiagnosticproceduresNCCNGuideline和CSCO指南的建议中国临床肿瘤学会（CSCO）原发性肺癌诊疗指南2017.V15©2016ThermoFisherScientificCorporation.Allrightsreserved.ForResearchUseOnly.Notforuseindiagnosticprocedures液体活检的临床意义治疗方案选择疗效监控复发监控血液样本、手术样本及术后三天样本3weeks为周期取样，持续6-8轮3-6个月为周期取样Solidtumorsample•中等灵敏度•价格适中•高灵敏度•低价•最高灵敏度•低价市场需求适用平台肿瘤患者疾病周期•一代测序：组织•NGS(0.1%to1%LOD)：组织&血液•数字PCR•NGS(0.1%LOD)•数字PCR•NGS(0.1%LOD)Liquidbiopsysample早期诊断(Screening)Liquidbiopsysample血液样本•高灵敏度•低价•NGS(largepan-cancerpanels)*PiperJaffray,The2015LiquidBiopsyReport,September20156©2016ThermoFisherScientificCorporation.Allrightsreserved.ForResearchUseOnly.Notforuseindiagnosticprocedures•对检测灵敏度要求高cfDNA中•样本间差异大，早期患者ctDNA的含量低•对检测灵敏度要求高ctDNA丰度变化大ctDNA突变比例低检测目的不同•需要不同的检测方案•定性or定量•单基因or多基因检测结果解读•需要医学的解读•需要相应指南规范解读液体活检所面临的挑战7©2016ThermoFisherScientificCorporation.Allrightsreserved.ForResearchUseOnly.Notforuseindiagnosticprocedures最接近临床转化的NGS液体活检应用治疗方案选择疗效监控复发监控血液样本、手术样本及术后三天样本3weeks为周期取样，持续6-8轮3-6个月为周期取样Solidtumorsample•中等灵敏度•价格适中•高灵敏度•低价•最高灵敏度•低价市场需求适用平台肿瘤患者疾病周期•一代测序：组织•NGS(0.1%to1%LOD)：组织&血液•数字PCR•NGS(0.1%LOD)•数字PCR•NGS(0.1%LOD)Liquidbiopsysample早期诊断(Screening)Liquidbiopsysample血液样本•高灵敏度•低价•NGS(largepan-cancerpanels)*PiperJaffray,The2015LiquidBiopsyReport,September20158©2016ThermoFisherScientificCorporation.Allrightsreserved.ForResearchUseOnly.NotforuseindiagnosticproceduresOncomine™液体活检试剂盒：一管血实现多基因0.1%低频突变检测肺癌LungcfDNAAssay11genesHotspots肺癌LungcfTNAAssay12genesDNAandRNAHotspotsCNVs,Fusion泛癌种Pan-cancercfTNAAssay52genesDNAandRNAHotspots,CNVsFusions,TumorSuppressor乳腺癌BreastcfDNAAssayv212genesHotspotsCNVsTP53结直肠癌ColoncfDNAAssay14genesHotspots乳腺癌BreastcfDNAAssay10genesHotspots9©2016ThermoFisherScientificCorporation.Allrightsreserved.ForResearchUseOnly.Notforuseindiagnosticprocedures晚期驱动基因阳性NSCLC的液体活检：治疗方案选择及耐药检测中国临床肿瘤学会（CSCO）原发性肺癌诊疗指南2017.V110©2016ThermoFisherScientificCorporation.AllrightsreservedF.orResearchUseOnly.NotforuseindiagnosticproceduresOncomine™lungcfTNAAssay：NSCLC突变、融合和CNV液体活检cfDNA&cfRNAIonTorrent™Oncomine™LungCell-FreeTotalNucleicAcidResearchAssay(单个文库)ALKBRAFEGFRERBB2KRASMAP2K1METNRASPIK3CARETROS1TP53125811169GenesAmpliconsGeneswithkeyhotspotmutationsHotspotSNVsandindels4911©2016ThermoFisherScientificCorporation.Allrightsreserved.Fusions:ALK，RET,ROS1基因突变类型靶向药物EGFRExon18-21突变（敏感&耐药）吉非替尼、厄洛替尼、埃克替尼、阿法替尼、达克替尼、奥希替尼ALK融合（敏感）/突变（耐药）克唑替尼、色瑞替尼、艾乐替尼、Brigatinib、LorlatinibROS1融合（敏感）克唑替尼BRAFV600E（敏感）达拉非尼联合曲美替尼MET扩增/14外显子跳跃突变（敏感）克唑替尼、沃利替尼（和记黄埔，临床阶段）ERBB2（HER2）Exon20突变（敏感）阿法替尼RET融合（敏感）卡博替尼、凡德他尼KRAS/NRASG12X,G13X,Q61X（耐药）不合适用TKISNVLODdownto0.1%with20nginput,samesensitivityandspecificityFusions:ALK，RET,ROS1—at1%LODCNVMET，METexon14skippingIV期结直肠癌治疗方案药物作用机制基因检测贝伐珠单抗（安维汀）联合5-氟尿嘧啶（化疗）抗血管Th成（VEGF）无西妥昔单抗（爱必妥）/帕尼单抗联合伊立替康（化疗）抑制表皮Th长因子（EGFR）KRAS/NRAS/BRAF（野Th型敏感）帕母单抗/纳武单抗抑制PD-1与PD-L1结合（免疫治疗）dMMR（DNA错配修复基因缺陷）MSI-H（微卫星不稳定）晚期结直肠癌的治疗方案结直肠癌靶向治疗耐药检测•Prevalenceofgeneticalterationsassociatedwithdenovoresistancetoanti-EGFRtherapiesinmCRC.•结直肠癌96%的靶向治疗（西妥昔单抗和帕尼单抗）耐药发Th与KRAS，NRAS，BRAF，EGFR的突变相关；•EGFR胞外结构域的变体（s492r）提示患者会对西妥昔单抗治疗产Th抗性，对帕尼单抗治疗则不然；SandraMisaleetal.CancerDiscovery2014;4:1269-128012©2016ThermoFisherScientificCorporation.Allrightsreserved.晚期结直肠癌的靶向治疗：CSCO指南2017版13©2016ThermoFisherScientificCorporation.Allrightsreserved.Oncomine™Col