Innovations therapy: mammalian target of rapamycin (mTOR) inhibitors for the treatment of neuroendocrine tumors

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare neoplasms that require a multidisciplinary approach for an optimal management. The lack of effectiveness of traditional DNA-damaging agents has led to the exploration of new targeted drugs in order to exploit phenotypical features of GEP-NET therapy. However, due to the orphan setting of these tumors, deeper characterization of molecular features and pathways that characterize cell growth, apoptosis, angiogenesis, and invasion are lacking, particularly genetic mutations or epigenetic alterations that generate oncogenic dependency or even addiction. The PI3K-AKT-mTOR pathway has been implicated as having a crucial role in GEP-NETs not only due to the overexpression of several growth factors and their receptors that finally activate this axis but also hereditary syndromes with constitutive activation of the mTOR pathway with high incidence of GEP-NETs. In this article, we aim to review the recent development of the main molecules that target mTOR complex and have showed promising activity in the treatment of GEPNETs.