Somatostatin and somatostatin receptors: from basic concepts to clinical applications.

Somatostatin (SS) and SS receptors (ssts) are broadly expressed in the human body where they exert many physiological actions. Moreover, they can be expressed in many pathological tissues. Particularly, a high density of ssts has been described in human neuroendocrine tumors (NETs). SS and ssts have a therapeutic and diagnostic value in several clinical conditions. For this reason stable SS-analogues have been developed. Among SS-analogues, octreotide, octreotide long-acting-release (LAR), lanreotide-sustained-release (SR) and lanreotide autogel (ATG) are approved for clinical use and pasireotide is in a late phase of clinical development. Presently, the SS-analogues are the standard treatment option for acromegalic patients and play a prominent role in the symptomatic control of patients with gastroenteropancreatic-neuroendocrine tumors (GEP-NETs). SS-analogues are able to control hormonal hypersecretion and reduce tumoral growth in the majority of cases. However, some patients are resistant to SS-analogue treatment and other patients (often GEP-NETs), after a variable period of treatment, develop tachyphylaxis to these compounds. The mechanisms behind this treatment resistance or tachyphylaxis are presently under investigation. The understanding of these mechanisms might help to develop new treatment modalities for patients not responding to the currently available SS-analogues. The high tumoral expression level of ssts, characteristic of many NETs, has been the rational to develop radiolabelled SS-analogues to visualize sst-expressing tumors and to treat unresectable tumors. Indeed, SS-analogues coupled with (111)In are used to perform sst-scintigraphy, which is a very useful first-line imaging technique in the diagnosis and follow-up of GEP-NETs. Moreover, SS-analogues conjugated to (111)In or to other radioisotopes, such as (177)Lu or (90)Y, have promising effects in the treatment of advanced NETs. ssts are expressed in some non-neuroendocrine tumors as well and in some non-tumoral diseases, suggesting that SS-analogues might have a role in the diagnosis and treatment of these pathological conditions as well. The development of novel SS-analogues with new pharmacokinetic and pharmacodynamic characteristics may further improve the clinical applications of such compounds. Copyright 2010 Elsevier B.V. All rights reserved.