Basal Cell Carcinoma From the Molecular Understanding of the Pathogenesis to Targeted Therapy of Progressive Disease英文文献资料.docVIP

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Basal Cell Carcinoma From the Molecular Understanding of the Pathogenesis to Targeted Therapy of Progressive Disease英文文献资料.doc

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Basal Cell Carcinoma From the Molecular Understanding of the Pathogenesis to Targeted Therapy of Progressive Disease英文文献资料

HindawiPublishingCorporation JournalofSkinCancer Volume2011,ArticleID650258,8pages doi:10.1155/2011/650258 ReviewArticle BasalCellCarcinoma:FromtheMolecularUnderstandingof thePathogenesistoTargetedTherapyofProgressiveDisease DanielaG¨oppner andMartinLeverkus 1 2 1 2 DepartmentofDermatologyandVenerology,Otto-von-Guericke-UniversityMagdeburg,LeipzigerSt.44,39120Magdeburg,Germany DepartmentofDermatology,Venerology,andAllergology,MedicalFacultyMannheim,Ruprecht-Karls-UniversityofHeidelberg, Theodor-Kutzer-Ufer1-3,68167Mannheim,Germany CorrespondenceshouldbeaddressedtoMartinLeverkus,Martin.Leverkus@medma.uni-heidelberg.de Received8July2010;Accepted21September2010 AcademicEditor:TorelloLotti Copyright?2011D.G¨oppnerandM.Leverkus. This is an open access article distributed under the Creative Commons AttributionLicense,whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalworkis properlycited. Duetointensi?edresearchoverthepastdecade,theHedgehog(HH)pathwayhasbeenidenti?edasapivotaldefectimplicated inroughly25%ofallcancers.Asoneofthemostfrequentcancerworldwide,thedevelopmentofBasalcellcarcinoma(BCC) duetoactivationoftheHHpathwayhasbeenconvincinglydemonstrated.Thusthediscoveryofthiscentraltumor-promoting signallingpathwayhasnotonlyrevolutionizedtheunderstandingofBCCcarcinogenesisbuthasalsoenabledthedevelopment ofacompletelynoveltherapeuticapproach.Targetingjustafewofseveralpotentialmutations,HHinhibitorssuchasGDC- 0449 achieved already the ?rst promising results in metastatic or locally advanced BCC. This paper summarizes the current understandingofBCCcarcinogenesisanddescribesthecurrent“mechanism-based”therapeuticstrategies. 1.Introduction cancer. Moreover, we discuss current and future therapies thatareneededinordertoallowe?cienttreatmentofBCC incomplicatedlocalization,inpatientswithmultipletumors or genetic disease predisposing for BCC development, or patientsthatarenoteligibleforsurgery. BCC,themostcommonlydiagno