title: Everolimus  for the treatment of pancreatic neuroendocrine tumors.
abstract: BACKGROUND
  Pancreatic neuroendocrine tumors (PNET) represent the second most common primary malignancy of the pancreas. Until recently, therapeutic options for advanced PNET have been limited.
  
  
  METHODS
  A recently published Phase III clinical trial demonstrated striking therapeutic activity of the mTOR inhibitor everolimus in advanced PNET and led to its approval for this indication by the FDA. This review discusses this landmark discovery in the context of currently available therapeutic options, pathophysiology and molecular genetics of PNET.
  
  
  CONCLUSIONS
  The approval of everolimus for the treatment of PNET marks a major step forward in the clinical management of this disease and represents a notable example of the successful translation of a targeted therapy that was initially developed based on findings at the lab bench, into everyday clinical practice. These results encourage hopes that the overall therapeutic efficacy of such approaches can be further enhanced by the introduction of combinatorial regimens, simultaneously targeting more than one oncogenic signaling pathway, as well as by stratification of patients based on the individual genetic setup of their tumors.
authors.affiliation: University Hospital of Bonn, Center of Integrated Oncology Cologne-Bonn, Department of Internal Medicine 3, Biomedizinisches Zentrum, Room 3G 024, Sigmund-Freud-Str. 25, D-53127 Bonn, Germany. georg.feldmann@uni-bonn.de
authors.forename: Georg
authors.initials: G
authors.lastname: Feldmann
authors.forename: Savita
authors.initials: S
authors.lastname: Bisht
authors.forename: Ute
authors.initials: U
authors.lastname: Schütte
authors.forename: Jens
authors.initials: J
authors.lastname: Haarmann
authors.forename: Peter
authors.initials: P
authors.lastname: Brossart
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000068338:Everolimus; D006801:Humans; D018358:Neuroendocrine Tumors / Q000188:drug therapy*; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors
chemical_list: D000970:Antineoplastic Agents; D000068338:Everolimus; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus