In our current study, we observed that the PI3K/Akt compensatory activation in response to LEE011 was reversed after the combination of LEE011 with trametinib or SCH77284 in a cell-line-dependent manner, as shown by the decreases in pAKT, pS6K, and p4EBP levels after the combination treatment of LEE011 with SCH772984 or trametinib; however, the existence of tumor heterogeneity might explain some of the discordant results. This evidence concerns the gene AKT1 and neoplasm.