cell lines were all insensitive to inhibition of AKT alone. Cells were treated with PD0325901, a selective, allosteric inhibitor order Ivacaftor of MEK1/2, to determine the reliability of the RAS/RAF altered cohort on MAP kinase pathway activation. PD901 potently down-regulated ERK phosphorylation in every cell lines examined but only inhibited the proliferation of the RAS/ RAF altered cells. Despite their dependence on MEK for proliferation, induction of cell death was not observed with PD901 treatment. In tumors with activation of AKT and ERK signaling, inhibition of both is demonstrated to be necessary for effective antitumor activity. Neither PD901 nor 2 uM of MK2206 induced apoptosis in OVCAR 5 cells at 72 h. Treatment with higher levels of MK2206 resulted in a marginal increase in cell death, which was significantly enhanced by concurrent MEK inhibition. More over, cotreatment of PD901 and MK2206 synergistically paid down the Human musculoskeletal system phosphorylation of p70S6K, S6, and 4EBP1 and decreased cyclin D3 expression. Co treatment with the pancaspase inhibitor ZVAD FMK or QVD OPH abrogated the increase in cell death observed with mixture treatment, confirming this effect was the result of synergistic induction of apoptosis. A similar induction of apoptosis and inhibition of downstream signaling was also noticed in OVCAR 5 cells following concomitant knockdown of KRAS expression by therapy and siRNA with MK2206 at 10 uM. Finally, consistent with the in vitro effects, enhanced anti-tumor activity was observed with the mixture of PD901 and MK2206 in mice bearing established RAS mutant OVCAR 5 xenografts. Induction of cell order Tipifarnib death was significantly higher in OVCAR 5 cells when PD901 was combined with container AKT inhibitor MK2206 as compared to the isoform selective inhibitor AKTi 1/2. We stably contaminated OVCAR 5 cells with lentiviral shRNAs targeting AKT3 or a control, to further establish the role of AKT3 to advertise cell survival in this context. Concurrent therapy with AKTi 1/2 and PD901 led to induction of cell death only in OVCAR 5 cells with steady expression of AKT3 shRNAs, but not in cells infected with a scrambled control hairpin. These suggest that AKT3 may operate redundantly with AKT1 and AKT2 to promote the survival of a subset of ovarian cancers. The ovarian cancer cell line cell mirrors, but doesn’t fully reflect, the genomic diversity of ovarian cancers One major limitation of the utilization of cell line models is that they may not recapitulate the genomic diversity of the human disease and therefore their value in predicting drug response may be limited. We ergo analyzed the mRNA and genomic expression data generated from the TCGA to determine the incidence of the cell line derived spectrum of genomic alterations in 316 high quality serous ovarian tumors.