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ID:34975215
大小:1.23 MB
页数:9页
时间:2019-03-15
《癌症-姜海A mammalian functional-genetic approach to characterizing cancer therapeutics.pdf》由会员上传分享,免费在线阅读,更多相关内容在学术论文-天天文库。
1、articlepublishedonline:26december2010;
2、doi:10.1038/nchembio.503amammalianfunctional-geneticapproachtocharacterizingcancertherapeuticshaiJiang1,Justinrpritchard1,richardtWilliams2,douglasalauffenburger1,3&michaelthemann1*Identifyingmechanismsofdrugactionremain
3、safundamentalimpedimenttothedevelopmentandeffectiveuseofchemother-apeutics.HerewedescribeanRNAinterference(RNAi)–basedstrategytocharacterizesmall-moleculefunctioninmammaliancells.ByexaminingtheresponseofcellsexpressingshorthairpinRNAs(shRNAs)toadiverseselecti
4、onofchemotherapeutics,wecouldgenerateafunctionalshRNAsignaturethatwasabletoaccuratelygroupdrugsintoestablishedbiochemicalmodesofaction.This,inturn,providedadiverselysampledreferencesetforhigh-resolutionpredictionofmechanismsofactionforpoorlycharacterizedsmall
5、molecules.WecouldfurtherreducethepredictiveshRNAtargetsettoasfewaseightgenesand,byusinganewlyderivedprobability-basednearest-neighborsapproach,couldextendthepredictivepowerofthisshRNAsettocharacterizeadditionaldrugcategories.Thus,afocusedshRNAphenotypicsignat
6、urecanprovideahighlysensitiveandtractableapproachforcharacterizingnewanticancerdrugs.hemotherapyremainsthefrontlinetherapyforsystemicdrugaction,thesestrategiesretainaleveloftechnicalvariabilitymalignancies.However,drugdevelopmenthasbeenseverelyandresourcerequ
7、irementthatlimitsbothdisseminateduseandChamperedbyaninabilitytoefficientlyelucidatemecha-overallefficacy.HerewereportatractableRNAi-basedapproachnismsofdrugaction.Thislimitsboththedevelopmentofmodifiedthatrepresentsasimpleyetpowerfulplatformfordrugscreeningco
8、mpoundswithimprovedefficacyandthecapabilitytopredictandcharacterization.mechanismsofdrugresistanceandselectoptimalpatientpopu-lationsforagivenagent.Althoughdrug-targetinteractionshaveRESULTStraditionallybeenexaminedusingbiochemicalapproaches1,anum-Clusteringd
9、rugsviashRNA-mediatedphenotypesberofgeneticstrategieshavebeendevelopedtoidentifypathwaysWehypothesizedthatRNAi-mediatedsuppressionofcelldeathtargetedbyuncharacterizedsmallmolecules.Awell-
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