Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Apr 15, 2016; 8(4): 389-401
Published online Apr 15, 2016. doi: 10.4251/wjgo.v8.i4.389
Medical treatment for gastro-entero-pancreatic neuroendocrine tumours
Rossana Berardi, Francesca Morgese, Mariangela Torniai, Agnese Savini, Stefano Partelli, Silvia Rinaldi, Miriam Caramanti, Consuelo Ferrini, Massimo Falconi, Stefano Cascinu
Rossana Berardi, Francesca Morgese, Mariangela Torniai, Agnese Savini, Silvia Rinaldi, Miriam Caramanti, Consuelo Ferrini, Stefano Cascinu, Department of Medical Oncology, Università Politecnica delle Marche, 60126 Ancona, Italy
Stefano Partelli, Massimo Falconi, Chirurgia del Pancreas, Ospedale San Raffaele IRCCS, Università Vita e Salute, 20132 Milano, Italy
Author contributions: Berardi R was responsible for manuscript conception, revising literature and writing the paper and had the final responsibility to submit for publication; Morgese F, Torniai M, Savini A, Partelli S, Rinaldi S, Caramanti M, Ferrini C, Falconi M and Cascinu S contributed to performing research, analysing literature data, writing the paper; all authors had contributed to the manuscript and approved the final version.
Conflict-of-interest statement: All authors declare that they have no competing interests.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Rossana Berardi, MD, Department of Medical Oncology, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I - GM Lancisi - G Salesi di Ancona, Via Conca 71, 60126 Ancona, Italy.
Telephone: +39-071-5965715 Fax: +39-071-5965053
Received: May 24, 2015
Peer-review started: May 25, 2015
First decision: September 14, 2015
Revised: January 18, 2016
Accepted: February 14, 2016
Article in press: February 16, 2016
Published online: April 15, 2016

Gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NENs) represents a various family of rare tumours. Surgery is the first choice in GEP-NENs patients with localized disease whilst in the metastatic setting many other treatment options are available. Somatostatin analogues are indicated for symptoms control in functioning tumours. Furthermore they may be effective to inhibit tumour progression. GEP-NENs pathogenesis has been extensively studied in the last years therefore several driver mutations pathway genes have been identified as crucial factors in their tumourigenesis. GEP-NENs can over-express vascular endothelial growth factor (VEGF), basic-fibroblastic growth factor, transforming growth factor (TGF-α and -β), platelet derived growth factor (PDGF), insulin-like growth factor-1 (IGF-1) and their receptors PDGF receptor, IGF-1 receptor, epidermal growth factor receptor, VEGF receptor, and c-kit (stem cell factor receptor) that can be considered as potential targets. The availability of new targeted agents, such as everolimus and sunitinib that are effective in advanced and metastatic pancreatic neuroendocrine tumours, has provided new treatment opportunities. Many trials combing new drugs are ongoing.

Keywords: Neuroendocrine neoplasms of the gastro-entero-pancreatic system, Chemotherapy, Targeted agents, Somatostatin analogues, Everolimus, Sunitinib

Core tip: In this review, recent evidences in the biology and pathology of neuroendocrine neoplasms of the gastro-entero-pancreatic system were analysed, focusing on new biological perspectives of medical treatment. The evidence-based data of new-targeted drugs and the new molecular knowledge are summarized looking at the basis for future studies.