title: Translational Diagnostics and Therapeutics in Pancreatic Neuroendocrine Tumors.
abstract: Pancreatic neuroendocrine tumors (PNET) are rare tumors, but have been increasing in incidence. Although typically thought of as indolent, more than half of patients present with metastatic disease. For many years, the only mutations commonly known in these tumors were those in the MEN1 gene. Recently, the genetics underlying PNETs have been further defined through exome sequencing. The most frequent alterations found in sporadic PNETs are in MEN1, DAXX/ATRX, and a variety of genes in the mTOR pathway. Confirmation of these mutations has prompted trials with a number of drugs active in these pathways, and two drugs were eventually approved in 2011-sunitinib and everolimus. New data additionally identify the MET and CD47 receptors as potential novel drug targets. Yet despite improvements in progression-free survival with sunitinib and everolimus, further studies defining when to use these agents and factors associated with limitations in their utility are needed. As more discoveries are made in the laboratory that elucidate additional molecular mechanisms important in the initiation and metastasis of PNETs, continued efforts to translate these discoveries into distinct new therapies will be needed to improve patient survival. Clin Cancer Res; 22(20); 5022-9. ©2016 AACR SEE ALL ARTICLES IN THIS CCR FOCUS SECTION, "ENDOCRINE CANCERS REVISING PARADIGMS".
authors.affiliation: Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, Iowa.
authors.forename: Jessica E
authors.initials: JE
authors.lastname: Maxwell
authors.affiliation: Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, Iowa.
authors.forename: Scott K
authors.initials: SK
authors.lastname: Sherman
authors.affiliation: Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, Iowa. james-howe@uiowa.edu.
authors.forename: James R
authors.initials: JR
authors.lastname: Howe
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D051928:CD47 Antigen / Q000235:genetics; D000068338:Everolimus / Q000627:therapeutic use; D006801:Humans; D007211:Indoles / Q000627:therapeutic use; D018358:Neuroendocrine Tumors / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics; D011758:Pyrroles / Q000627:therapeutic use; D000077210:Sunitinib; D058570:TOR Serine-Threonine Kinases / Q000235:genetics
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D051928:CD47 Antigen; C497894:CD47 protein, human; D007211:Indoles; C105373:MEN1 protein, human; D011518:Proto-Oncogene Proteins; D011758:Pyrroles; D000068338:Everolimus; C546842:MTOR protein, human; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met; D058570:TOR Serine-Threonine Kinases; D000077210:Sunitinib