8P Cdk4/6 inhibitor activity in metastatic bladder cancer cell lines is independently of RB1 status

platinum-basedchemotherapy.Varioustargetedtherapiesarebeingclinicallyandpreclinicallytestedforbladdercancermanagement.Metastaticbladdercancerhasbeenassociatedwithlossofcellcyclecontrol.TCGAanalysisalsorevealedthatTP53mutationsweremutuallyexclusiveintheirrelationshipwithoverexpressionandamplificationofMDM2,therebyresultingininactivationofp53functionin76%ofsamples.DefectsintheRBpathwayareanothermajormechanismsbywhichcellcyclecontrolislostinmetastaticbladdercancer.TheCDK4/6complexcombineswithcyclinD1toinhibitRBactivity.TherapeutictargetingofthiscompleximprovesoutcomeinERpositiveadvancedbreastcancer.