Predictive biomarker discovery through the parallel integration of clinical trial and functional genomics datasets 英文参考文献.docVIP
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Predictive biomarker discovery through the parallel integration of clinical trial and functional genomics datasets 英文参考文献
Swantonetal.GenomeMed2010,2:53
/content/2/8/53
CORRESPONDENCE
OpenAccess
Predictivebiomarkerdiscoverythroughthe
parallelintegrationofclinicaltrialandfunctional
genomicsdatasets
CharlesSwanton1,2*?,JamesMLarkin2?,MarcoGerlinger1,3?,AronCEklund4?,MichaelHowell1,GordonStamp1,2,
JulianDownward1,MartinGore2,PAndrewFutreal5,BernardEscudier6,FabriceAndre6,LaurenceAlbiges6,
BenoitBeuselinck7,StephaneOudard7,JensHoffmann8,BalázsGyorffy9,ChrisJTorrance10,KarenABoehme11,
HansjuergenVolkmer11,LuisellaToschi12,BarbaraNicke12,MarleneBeck4,ZoltanSzallasi4
Abstract
TheEuropeanUnionmulti-disciplinaryPersonalisedRNAinterferencetoEnhancetheDeliveryofIndividualised
CytotoxicandTargetedtherapeutics(PREDICT)consortiumhasrecentlyinitiatedaframeworktoacceleratethe
developmentofpredictivebiomarkersofindividualpatientresponsetoanti-canceragents.Theconsortiumfocuses
ontheidentificationofreliablepredictivebiomarkerstoapprovedagentswithanti-angiogenicactivityforwhich
noreliablepredictivebiomarkersexist:sunitinib,amulti-targetedtyrosinekinaseinhibitorandeverolimus,amam-
maliantargetofrapamycin(mTOR)pathwayinhibitor.Throughtheanalysisoftumortissuederivedfrompre-
operativerenalcellcarcinoma(RCC)clinicaltrials,thePREDICTconsortiumwilluseestablishedandnovelmethods
tointegratecomprehensivetumor-derivedgenomicdatawithpersonalizedtumor-derivedsmallhairpinRNAand
high-throughputsmallinterferingRNAscreenstoidentifyandvalidatefunctionallyimportantgenomicortranscrip-
tomicpredictivebiomarkersofindividualdrugresponseinpatients.PREDICT’sapproachtopredictivebiomarker
discoverydiffersfromconventionalassociativelearningapproaches,whichcanbesusceptibletothedetectionof
chanceassociationsthatleadtooverestimationoftrueclinicalaccuracy.Thesemethodswillidentifymolecular
pathwaysimportantforsurvivalandgrowthofRCCcellsandparticulartargetssuitablefortherapeuticdevelop-
ment.Importantly,ourresultsmayenableindividualizedtreatmentofRCC,reducingineffectivetherapyindrug-
resistantdisease,leadingtoimprovedqualityoflifeandhig
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