These results suggested that a relief of a feedback inhibition of the RTK-IRS1-PI3K-AKT pathway was responsible for the reactivation of AKT after AKTi or AKTi plus MEKi treatment in the KRAS or BRAF mutant CRC cells, and the combination of RTKis and AKTi efficiently inhibited the reactivation of AKT and the cancer cell growth. This evidence concerns the gene AKT1 and colorectal carcinoma.