Concurrent treatment with palbociclib and trametinib resulted in the greatest inhibition of cell cycle machinery (i.e., pRb, FOXM1, PLK1, cyclin D1) in lysate collected from a subset of tumor-bearing mice sacrificed after 3 days of treatment (Supplementary Fig. 5E) and conferred the greatest decrease of Ki67 staining in tumor tissue (Fig. 4D). Here, RB1 is linked to neoplasm.