Combined targeting of AKT and SGK completely inhibits proliferation of PI3K-active cancer cells. A-B dose-response plots showing the effect of SGK1 depletion on the efficacy of PI3K targeting. Dox+ values are shown as ratio to completely untreated cells in A, and as ratio to doxycycline-treated, GDC-0941-untreated cells in B. C, Western blot analysis of the phosphorylation of AKT and S6 in the THJ16T and T4888M cells upon 6 hours treatment with the indicated inhibitors at concentrations corresponding to EC75-EC90 as single drug. D, pharmacological co-targeting of AKT and SGK at a constant inhibitors ratio, showing synergistic interaction between the two compounds. E, long-term treatment of T4888M cells with the indicated inhibitors, showing progressive resistance to PI3K inhibition, and complete growth suppression with combined AKT and SGK inhibition.