The potentially causal role of PTEN in determining the functional outcome of combined MEK and mTOR inhibition was assessed in an isogenic colon cancer cell line model, differing only for PTEN status: Fig. 2D,E shows the growth inhibitory response (top panel) and pharmacologic interactions (expressed as combination index - CI - versus fraction affected, bottom panel) observed with Trametinib and Everolimus in the X-MANTM isogenic HCT116 cell lines. This evidence concerns the gene PTEN and malignant colon neoplasm.