Our results demonstrate for the first time that inhibiting glutamine utilization in tumor cells with constitutive activation of the PI3Kinase/Akt pathway [43, 46], induces cell death by GCN2-mediated triggering of a TRAIL-R2/FADD/Caspase-8 apoptotic pathway that requires amplification through the mitochondria. This evidence concerns the gene EIF2AK4 and neoplasm.