A MTT cell viability assays of UM cell lines treated with MEKi (trametinib, 5 nM) alone, CDK4/6i (palbociclib, 0.5 μM) alone, or the combination (trametinib + palbociclib) for 7 days (*p<0.05, **p<0.005) (n=3). B Downregulation of cell cycle proteins following MEKi + CDK4/6i treatment. UM cell lines treated with single agent or combination of MEKi (PD0325901, 5nM) and CDK4/6i (palbociclib, 0.5 μM) for 48 hours. Heatmap of median centered log2-transformed average group expression RPPA data for antibodies both differentially expressed (Storey q-value < 0.05, ratio >50%) and up or downregulated in at least two cell lines between combination or DMSO treated samples. C Western blot analysis of UM cell lines treated with single agent or combination of MEKi (PD0325901, 5 nM) and CDK4/6i (palbociclib, 0.5 μM) for 48 hours. Representative blots from triplicate experiments are shown.