OncogenicTranscriptionFactors:CornerstonesofInflammation-LinkedPancreaticCarcinogenesisSandraBaumgart1,VolkerEllenrieder1,andMartinE.Fernandez-Zapico21SignalingandTranscriptionLaboratory,DepartmentofGastroenterology,Philipps-UniversityofMarburg,D-35043Marburg,Germany2SchulzeCenterforNovelTherapeutics,DivisionofOncologyResearch,MayoClinic,Rochester,MN55905,USAAbstractTranscriptionfactorsareproteinsthatregulategeneexpressionbymodulatingthesynthesisofmessengerRNA.Sincethisprocessisfrequentlyonedominantcontrolpointintheproductionofmanyproteins,transcriptionfactorsrepresentthekeyregulatorsofnumerouscellularfunctions,includingproliferation,differentiation,andapoptosis.Pancreaticcancerprogressionischaracterizedbytheactivationofinflammatorysignalingpathwaysconvergingonalimitedsetoftranscriptionfactorsthatfine-tunegeneexpressionpatternscontributingtothegrowthandmaintenanceofthesetumors.Thus,strategiestargetingthesetranscriptionalnetworksactivatedinpancreaticcancercellscouldblocktheeffectsofupstreaminflammatoryresponsesparticipatinginpancreatictumorigenesis.Inthisarticlewereviewthisfieldofresearchandsummarizecurrentstrategiestotargetoncogenictranscriptionfactorsandtheiractivatingsignalingnetworksinthetreatmentofpancreaticcancer.Keywordstranscriptionfactors;pancreaticcancer;inflammation;therapyOncogenictranscriptionfactorsarefinaleffectorsofinflammatorysignallingpathwaysduringpancreaticcarcinogenesisPancreaticcancer,oneofthemostdevastatingmalignancies,istriggeredbygeneticandepigeneticalterationsleadingtotheaberrantactivationofkeyoncogenesandinactivationoftumoursuppressorpathways,andconsequentlyconfertransformingcellswithagrowthandsurvivaladvantageovernormalcells.ThemostcommongeneticabnormalityinpancreaticcanceristheactivatingmutationofKRAS,whichisaninitialkeyeventinpancreaticcarcinogenesisandfoundinvirtuallyallinvasivelygrowingtumors1.However,mutationofKRASaloneisnotsufficientforfullneoplasticprogression,andinsteadadditionalabnormalities(e.g.deletionsoftumorsuppressorgenes)...
