CDK4 and colorectal carcinoma: This data also complements the recent report of the combination of palbociclib and trametinib in KRAS-mutant CRC PDX models [63], but demonstrates that inhibition of phospho-S6 is a potential pharmacodynamic biomarker, and uniquely demonstrates that this inhibition is synergistic with the combination of CDK4/6 and MEK inhibitors in a broader number and mutational diversity of cell lines, including “atypical” KRAS A146T mutant CRC PDX models.