For example, a selective MEK inhibitor was shown to induce activation of AKT in basal-like breast cancer models and in pancreatic cancer cell lines.35,36,37 In addition, PI3K/AKT pathway activation caused resistance to MEK inhibitors in mutant KRAS cells.38 Indeed, we validated that knockdown of KRAS alone could not down-regulate the ERK phosphorylation in DLD1 and that it led to only limited growth inhibition, which is consistent with an earlier finding reported by Singh et al. 39 (see Supplementary Figure S3b). Here, AKT1 is linked to familial pancreatic carcinoma.