Everolimus and mTOR inhibition in pancreatic neuroendocrine tumors

Pancreatic neuroendocrine tumors are rare and the majority of patients present in the advanced stage. Over the past few decades, treatment for patients with metastatic well- or moderately differentiated pancreatic neuroendocrine tumors have not significantly impeded tumor progression nor improved survival. However, recent mapping of intracellular signaling pathways promoting tumor proliferation, growth, and angiogenesis has presented mammalian target of rapamycin (mTOR) as a potential target within the phosphatidylinositol 3-kinase-Akt pathway. With the development of the new-generation mTOR inhibitor everolimus, a series of clinical trials over the last 5 years have demonstrated significant benefit in delaying tumor progression. This review focuses on the mechanism of mTOR inhibition and traces the development of clinical evidence for the use of mTOR inhibitors in well- to moderately differentiated advanced pancreatic neuroendocrine tumors.