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1、DevelopmentofMolecularlyTargetedTherapiesinBiliaryTractCancers:ReassessingtheChallengesandOpportunities12AndrewX.Zhu,andAramF.HezelBiliarytractcancers(BTCs),whichencompassintra-andextrahepaticcholangiocarcino-masaswellasgallbladdercarcinomas,areagenetical
2、lydiversecollectionofcancers.MostpatientswithBTCwillpresentwithunresectableormetastaticdisease.Althoughthestand-ardsystemicchemotherapyapproachesareemerging,theprognosisremainspoor.Devel-opmentofmolecularlytargetedtherapiesinadvancedBTCremainschallenging.
3、Recentearly-stageclinicaltrialswithtargetedtherapiesappearpromising,althoughtherelation-shipsbetweensubsetsofpatientswithpositiveresponsestotherapyandtumorgeneticsremainunexplored.Herewesummarizetherelevantmolecularpathogenesis,recentandongoingclinicaltri
4、alswithtargetedagents,andthekeyissuesinclinicaltrialdesigninBTC.(HEPATOLOGY2011;53:695-704)iliarytractcancers(BTCs)includeaspectrumAlthoughmolecularlytargetedtherapieshaveemergedBofinvasiveadenocarcinomasencompassingbothasthestandardtreatmentseitheraloneo
5、rincombinationcholangiocarcinoma(CC),usedtorefertocan-withchemotherapyorradiation,inmanycancertypes,cersarisingintheintrahepatic,perihilar,ordistalbiliarythedevelopmentoftargetedagentsinBTChasencoun-2,3tree,aswellascarcinomaarisingfromthegallbladderteredm
6、anychallenges(Fig.1).First,themolecular(GBC).BTCischaracterizedbyearlylymphnodeandmechanismunderlyingthepathogenesisofBTCremainsdistantmetastasesand,asaresult,only10%ofpatientselusive;theearlystagesofthediseasearepoorlyunder-presentwithearly-stagediseasea
7、ndareconsideredcandi-stoodandthegeneticsofadvanceddiseasehaveyettobedatesforsurgicalresection,whichofferstheonlychancefullydefined.Second,BTCisaheterogeneousgroupofforcure.Inselectivecenters,livertransplantationmayberelatedbutdistinctdiseaseswithvariouscli
8、nicalfeaturesconsideredanoptionforearly-stagediseaseaswell.Theandlikelydifferentgeneticschanges.Third,BTCisrela-prognosisispoorforpatientswithlocallyadvancedortivelyrareandhasbeentraditionallylistedasan‘‘orphan’’met
