Fig. 5: Acquired biological resistance to MK-2206 is associated with biochemical AKT1 resistance that is not mediated by AKT mutation.

a MDA-MB-361 cells were chronically treated with 2 μM MK-2206 for 12 weeks. Surviving cells were removed from treatment and re-challenged with the indicated drugs for 18 h. Cells were lysed and lysates examined by immunoblot with the indicated antibodies. b Parental and MK-2206- resistant MDA-MB-361 cells cultured in MK-2206 (Res +) or not (Res −) were treated with the indicated doses of MK-2206. The fold change in cell numbers (left) and the fraction of dead cells (right) following 4 days of drug treatment is shown. c Parental and MK-2206-resistant MDA-MB-361 cells were treated with the indicated doses of ATP-competitive and allosteric AKT inhibitors. The fraction of dead cells following 4 days of drug treatment is shown (cell death %). d Parental and MK-2206-resistant MDA-MB-361 cells were treated with the indicated doses of various allosteric AKT inhibitors. The fold change in cell numbers (left) and the fraction of dead cells (right) following 4 days of drug treatment is shown. e Cells treated as in d were also lysed following 24 h of drug treatment, and lysates were examined by western blot using the indicated antibodies. f MDA-MB-361 cells were treated with various AKT inhibitors either alone or in combination 50 nM rapamycin. The fold change in cell numbers (top) and the fraction of dead cells (bottom) following 4 days of drug treatment is shown. n.s., not significant. *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001 and ****P ≤ 0.0001.