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For many years, the treatment of advanced pancreatic neuroendocrine tumors (pNETs) has been limited almost entirely to somatostatin analogs and streptozocin-based chemotherapy, with modest benefit. Increasing knowledge of the biologic features of pNETs has allowed the design of molecular-based clinical trials, which have taken a step forward in the management of these tumors. In this review, we discuss the molecular rationale for the development of everolimus for patients with advanced pNETs, critically review the clinical data obtained by the main studies in this setting, and discuss essential considerations based on recent findings in pNET biology for future drug development involving the phosphatidylinositol 3' kinase- AKT-mTOR pathway.

Critical appraisal of the role of everolimus in advanced neuroendocrine tumors of pancreatic origin