Thus, it has been demonstrated that a prolonged treatment of tumor cell lines or patients with rapamycin, an mTOR inhibitor, and its synthetic analogs (temsirolimus and everolimus) inhibits mTOR function but controversially, increases eIF4E phosphorylation and AKT activation, resulting in a mTOR-targeted therapy resistance through a compensatory feed-back mechanism between the AKT/mTOR pathway and MNK/eIF4E pathway [46,47,48,49]. This evidence concerns the gene AKT1 and neoplasm.