Table 1.

CIa by the Chou–Talalay method for selumetinib and MK-2206b

Cell lineCancer typeKRASPIK3CABRAFPTENCI: ED50CI: ED75CI: ED90
HCT116ColonG13DH1047RWTWT0.200.140.11
HCT15ColonG13DE545KWTWT0.120.120.12
HT29ColonWTP449TV600EWT0.680.730.82
A2058MelanomaWTWTV600EDel0.350.190.12
AsPC-1PancreaticG12DWTWTWT0.180.090.15
MIA-Pa-Ca2PancreaticG12CWTWTWT0.420.250.58
Calu-6LungQ61KWTWTWT0.250.200.18
HCI-H460LungQ61HE545KWTWT0.040.030.02
  • aCell Lines were studied across 2-fold serial dilutions spanning the IC50 for each cell line for each individual drug. Shown is the CI, which calculates the combination effects as a function of the slopes of the inhibition curves independent of any specific drug concentration.

  • bAn additional analysis was performed on an expanded set of colorectal cancer cell lines harboring either wild-type or mutant K-RAS, B-RAF, or PIK3CA, which were analyzed for sensitivity to MEKi or AKTi + MEKi. The results suggest that PIK3CA mutant status predicts resistance to single-agent MEKi treatment, whereas combination treatment of AKTi + MEKi reversed this effect. MEKi sensitivity was not altered in the presence of either wild-type or mutant K-RAS or B-RAF status in these lines.