title: Molecular pathogenesis and targeted therapy of sporadic pancreatic neuroendocrine tumors.
abstract: Over the past few years, knowledge regarding the molecular pathology of sporadic pancreatic neuroendocrine tumors (PNETs) has increased substantially, and a number of targeted agents have been tested in clinical trials in this tumor type. For some of these agents there is a strong biological rationale. Among them, the mammalian target of rapamycin inhibitor Everolimus and the antiangiogenic agent Sunitinib have both been approved for the treatment of PNETs. However, there is lack of knowledge regarding biomarkers able to predict their efficacy, and mechanisms of resistance. Other angiogenesis inhibitors, such as Pazopanib, inhibitors of Src, Hedgehog or of PI3K might all be useful in association or sequence with approved agents. On the other hand, the clinical significance, and potential for treatment of the most common mutations occurring in sporadic PNETs, in the MEN-1 gene and in ATRX and DAXX, remains uncertain. The present paper reviews the main molecular changes occurring in PNETs and how they might be linked with treatment options.
authors.affiliation: Digestive and Liver Disease Unit, Faculty of Medicine and Psychology, Sapienza University of Rome at S. Andrea Hospital, Rome, Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Capurso
authors.affiliation: Digestive and Liver Disease Unit, Faculty of Medicine and Psychology, Sapienza University of Rome at S. Andrea Hospital, Rome, Italy.
authors.forename: Livia
authors.initials: L
authors.lastname: Archibugi
authors.affiliation: Digestive and Liver Disease Unit, Faculty of Medicine and Psychology, Sapienza University of Rome at S. Andrea Hospital, Rome, Italy.
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Delle Fave
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D056970:Co-Repressor Proteins; D004265:DNA Helicases / Q000235:genetics; D057890:Epigenomics; D006801:Humans; D018832:Molecular Chaperones; D058990:Molecular Targeted Therapy; D009389:Neovascularization, Pathologic; D018358:Neuroendocrine Tumors / Q000188:drug therapy / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000502:physiology; D058570:TOR Serine-Threonine Kinases / Q000502:physiology; D000075924:X-linked Nuclear Protein
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D056970:Co-Repressor Proteins; C106985:DAXX protein, human; C105373:MEN1 protein, human; D018832:Molecular Chaperones; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D004265:DNA Helicases; C092332:ATRX protein, human; D000075924:X-linked Nuclear Protein
keywords: Genetics; Molecular; Mutation; Pancreatic neuroendocrine tumors; Targeted therapy