Appetecchia and Baldelli Journal of Experimental & Clinical Cancer Research 2010, 29:19 http://www.jeccr.com/content/29/1/19 R E V I E W Open Access Somatostatin analogues in the treatment of gastroenteropancreatic neuroendocrine tumours, current aspects and new perspectives Marialuisa Appetecchia*, Roberto Baldelli Abstract Gastroenteropancreatic neuroendocrine tumours (GEP NETs) are rare tumours that present many clinical features. They secrete peptides and neuroamines that cause distinct clinical syndromes, including carcinoid syndrome. How- ever, many are clinically silent until late presentation with mass effects. In 2000 the WHO developed a new classification which gives a better description of the characteristics and biologi- cal behaviour of the tumour. Surgical resection is the treatment of first choice for a patient with a GEP NET. In metastatic disease multiple thera- peutic approaches are possible. In these cases the goal is to improve quality of life and to extent survival. GEP NETs express somatostatin receptors (SSTRs), which are bound by somatostatin (SST) or its synthetic analogues, although the subtypes and number of SSTRs expressed is very variable. Somatostatin analogues are used frequently to control hormone-related symptoms while their anti-neoplastic activ- ity, even if it has not been widely studied and the regarding data are discordant, seems to result prevalently in tumour stabilisation. A few patients who fail to respond or cease to respond to standard SST analogues treatment seem to have a response to higher doses of these drugs. The use of higher doses of somatostatin analogues or the development of new subtype selective agonists and chimaeric somatostatin analogues, or pan-somatostatin will probably improve the clinical management of these patients. This review provides an update on the use of somatostatin analogues in the management of GEP NETs and discusses novel clinical strategies based on SSTR 2 gene transfer therapy. Introduction Gastroenteropancreatic neuroendocrine tumours (GEP NETs) are an heterogeneous group of relatively rare tumours, whose yearly incidence is 1.2-3.0 cases/100,000 inhabitants [1]. The database of the National Cancer Institute, Surveil- lance Epidemiology and End Results (SEER), mirroring the attention standards for US average patients, shows that the age-related incidence of small intestine and digestive tract carcinoids increased by 460% and 720% respectively, within a period of 30 years [2]. GEP NETs arise from local gastrointestinal stem totipotent cells, * Correspondence: appetecchia@ifo.it Endocrinology Unit, Regina Elena National Cancer Institute, Via Elio Chianesi, 53, Rome 00144, Italy rather than from the neural crest, as assumed at first [3]. According to the most recent histological classification of tumour features - based on diameter and presence/ absence of local or distance metastases - developed by the World Health Organization (WHO), tumours are classified as: a) well-differentiated neuroendocrine tumours; b) well- differentiated neuroendocrine carcinomas; c) poorly-differentiated neuroendocrine carcinomas; d) mixed exocrine-endocrine carcinomas [4,5]. In most cases, they are single isolated forms, but they can be multiple and part of familiar syndromes such as MEN 1 syndrome, von Hippel-Lindau disease and neu- rofibromatosis, type 1. These are mostly (well-differen- tiated) tumours with relatively slow growth, even if © 2010 Appetecchia and Baldelli; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.