文档介绍：该【在结直肠癌循环肿瘤细胞中KRAS和PIK3CA的突变以及EGFR异质性的研究 】是由【小落意心冢】上传分享，文档一共【28】页，该文档可以免费在线阅读，需要了解更多关于【在结直肠癌循环肿瘤细胞中KRAS和PIK3CA的突变以及EGFR异质性的研究 】的内容，可以使用淘豆网的站内搜索功能，选择自己适合的文档，以下文字是截取该文章内的部分文字，如需要获得完整电子版，请下载此文档到您的设备，方便您编辑和打印。在结直肠癌循环肿瘤细胞中KRAS和PIK3CA的突变以及EGFR异质性的研究Studyintroduction美国国家癌症综合治疗联盟()《结直肠癌临床实践指南》(2019)明确指出:(1)所有转移性结直肠癌患者都应检测KRAS基因状态;(2)只有KRAS野生型患者才建议接受EGFR抑制剂(如爱必妥和帕尼单抗)治疗。《非小细胞肺癌临床实践指南》(2019)明确指出:当KRAS基因发生突变时,不建议使用EGFR-TKIs靶向治疗药物。卫生部颁布的《结直肠癌诊疗规范(2019年版)》也明确指出:确定为复发或转移性结直肠癌时,检测肿瘤组织KRAS基因状态,以确定合适的治疗方案。1.?Amado?R?G,?Wolf?M,?Peeters?M,Van?Cutsem?E?et?al.?Journal?of?Clinical?Oncology.?April?.?Van?Cutsem?et?al.?ASCO?Annual?Meeting?2019:?abstract?.?Bokemeyer?et?al.?ASCO?Annual?Meeting?2019:?abstract?.?Lièvre?et?al.?J?Clin?Oncol?2019;26:374-.?美国FDA相关网站:,与配体结合后可引起下游信号传导通路的活化,如:KRASBRAF(4%–12%)RAS-RAF-MEK-Erk/MAPKPIK3CA(14%–20%)P13K-AKT-PKC-IKK在许多实体瘤中EGFR均有不同程度的表达,表达率最高为头颈部肿瘤,达95%—100%。CRC次之,为72%—89%,胃癌表达率为41%—64%,并且EGFR表达率高的肿瘤恶性度高,侵袭力强,预后差。而且在同一患者中不同的CTCs中,EGFR的表达也存在着异质性。[1]GoldsteinNS,:Implicationsforastandardizedscoring system[J].Cancer,2019,92(5):1331-1346.[2]BergstromJD,WestermarkB,-ceptorsignalingactivatesmetinhumananaplasticthyroidcarcinomacells[J].ExperimentalCellResearch,2000,259(1):292-299. [3]DenningMF,DlugoszAA,ChengC,-talkbetweenepidermalgrowthfactorreceptorandproteinkinaseCduringcalciumnduceddifferentiationofkeratinoytes[J].ExperimentalDermatology,2000,9(3):192-,cultureconditions,andfluorescenceinSituhybridizationanalysis(MCF,MDA-MB-468,BT-20,MDA-MB-468A)EnumerationofCTCsbyCS(FITC-thefourthchanneloftheCS)SamplepreparationformolecularanalysisafterCellSearchdetectionIsolationofCTCsbymicromanipulationWhole-GenomeAmplificationofDNAfromsingletumorcellswiththeGenomePlexkitWGAofDNAfromsingletumorcellswiththeGenomiPhikitIdentificationofEGFRgeneamplificationsbyPCRonWGAproducts(LINE1reference,EGFRtarget)Sequencingofsingle-cellWGAproductsMaterialsandMethodsResultsApplicabilityofWGAfromsingle-cellDNADetectionofEGFRexpressionandgeneamplificationsonsingleCTCsMutationalanalysisofsingleCTCsMutationsindownstreamgenesoftheEGFRsignalingpathwayDiscussionGenomiPhi-amplifiedDNAwasmoresuitableThemeanandmediangeneamplificationrates(--fold)determinedonGenomiPhiWGAproductsaresimilartothosedeterminedbyqPCRonDNAextracts(approximately107cells)andbyFISHanalysis(30-to40-fold)andareconsistentwithpublisheddataforMDA-MB-≥2CTCsin49%ofpatientswith mCRC(24of49)and22%ofpatientswithnmCRC(7of32).Theseresultsaresimilartopreviousfindingsrevealingdetectionratesof≥2CTCsin33%–61%ofpatientswithmCRC(17,30)and26%ofpatientswithnmCRC.[1]CohenSJ,PuntCJ,IannottiN,SaidmanBH,SabbathKD,GabrailNY,,progression-freesurvival,;26:3213–21.[2]SastreJ,MaestroML,PuenteJ,VeganzonesS,AlfonsoR,RafaelS,:;19:935–:1–%–90%asesweredescribedtobepositiveforEGFRexpression,CTCswithincreasedEGFRexpressionlevelscouldbedetectedinonly7of33(21%)CTC-positivepatients.[1]ShankaranV,ObelJ,:;15:157–(leftimages)correlateswithEGFRgeneamplificationratesdeterminedbyqPCRandFISH(righttables)withMCF-7(lowEGFRexpression=score0–1,),MDA-MB-468A(moderateEGFRexpression=score2,),BT-20(strongEGFRexpression=score3,),andMDA-MB-468(strongEGFRexpression=score3,/>30)