Putao Cen, Robert J AmatoDivision of Oncology, Department of Internal Medicine, University of Texas Health Science Center at Houston (Medical School), Houston, TXAbstract: Pancreatic neuroendocrine tumors (PanNETs) are frequently diagnosed at unresectable stage and remain a medical challenge. Everolimus (RAD001, Afinitor®, Novartis, Basel, Switzerland), an orally administered inhibitor of mammalian target of rapamycin (mTOR), was recently approved by the Food and Drug Administration to treat patients with advanced PanNETs. This review will examine the mechanism of action of everolimus, the function of mTOR and its inhibition, PanNETs and the mTOR pathway, and clinical trials of everolimus in PanNETs. Future investigations will focus on everolimus combination therapy to treat PanNETs and the discovery of predictive biomarkers for response to everolimus.Keywords: pancreatic neuroendocrine tumor, PanNETs, everolimus, RAD001, mTOR inhibitor, biomarker