The loss of negative feedback and inhibition of the IGF1R, which is normally exerted by phosphorylated ribosomal p70S6 kinase, following treatment with mTOR inhibitors in cancer, and the upregulation of insulin receptor substrate (IRS) 1/2, upon treatment with Akt inhibitors, leading to the activation of the PI3K-Akt and MAPK pathways, hints at the possibility of cross-talk between the two pathways and likely accounts for the reduced efficacy of these drugs [34, 154–159]. This evidence concerns the gene AKT1 and cancer.