The role of mTOR inhibitors in neuroendocrine tumors

There have been major developments in our understanding of the histopathological classification, genetics, molecular signaling pathways, and treatment of neuroendocrine tumors (NETs) over the last decade. The phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway is a promising target for well-differentiated NETs. The recent success of everolimus, an inhibitor of the mammalian target of rapamycin, is proof of principle that targeting this pathway will lead to improved outcomes in these patients. Novel therapies targeting angiogenesis, such as bevacizumab and sunitinib, are showing promise in NETs by improving progressionfree survival alone or in combination with mTOR inhibitors. There are an unprecedented number of ongoing clinical trials of innovative treatments for this disease, and the development of combination therapy will lead to better therapeutic outcomes.