A review of the use of somatostatin analogs in oncology

Abstract

Somatostatin is a neuropeptide produced by paracrine cells that are located throughout the gastrointestinal tract, lung, and pancreas, and is also found in various locations of the nervous system. It exerts neural control over many physiological functions including inhibition of gastrointestinal endocrine secretion through its receptors. Potent and biologically stable analogs of somatostatin have been developed. These somatostatin analogs show different efficacy on different receptors, and receptors are varyingly concentrated in specific tissues. Antitumor and antisecretory effects of somatostatin analogs in cancer have been shown in several in vivo and in vitro studies. However, these activities have not always yielded into clinically relevant patient outcome benefit. Somatostatin analogs are of clinical benefit in treating symptoms of ectopic hormone secretion (adrenocorticotropic hormone, growth hormone-releasing hormone) in lung cancer, without inducing a significant tumor response. They have also been shown to induce a statistically significant decrease in bone pain and increase in Karnofsky performance status in patients with metastatic prostate cancer. Somatostatin analogs alone or in combination with other agents have only limited antitumoral effect in breast cancer. In gastrointestinal cancers, studies have not shown an objective tumor response to somatostatin analogs except in endocrine tumors of the liver with symptomatic and biochemical improvement. In neuroendocrine tumors of the gastrointestinal system and pancreas, very high symptomatic and biochemical response rates have been achieved with somatostatin analogs. Antiproliferative activity has been clearly shown in metastatic midgut neuroendocrine tumors.

CXCL14-like Immunoreactivity Exists in Somatostatin-containing Endocrine Cells, and in the Lamina Propria and Submucosal Somatostatinergic Nervous System of Mouse Alimentary Tract

“…These somatostatin receptors are often targeted for the therapeutic treatment of various neuroendocrine tumors [ 42 ]. Although underling mechanisms of these two peptides-associating functions are not elucidated yet, it is worthy to note that clinically, both CXCL14 and somatostatin have antitumor activities [ 21 , 33 , 35 , 53 ]. Further studies on the genetic and protein expression profiles of CXCL14 in various neuroendocrine tumors may clarify the association of these two peptides and their antitumor mechanisms.…”

Presence of sst5TMD4, a truncated splice variant of the somatostatin receptor subtype 5, is associated to features of increased aggressiveness in pancreatic neuroendocrine tumors

“…These results further support the hypothesis of the potential interference of this variant in the putative signaling pathway of canonic non-truncated sst subtypes, as it has been proposed in earlier studies [ 18 ], as well as with angiogenic molecules, as also suggested by our present data. SSAs are known to exert an anti-angiogenic effect through their interaction with ssts, by inhibiting production and secretion of many angiogenic factors [ 10 , 11 ]. In this context, previous studies have reported that signaling through sst3 down-regulates VEGF production [ 29 ], that sst1 signaling inhibits endothelial proliferation, migration and neovascularization [ 32 , 50 ], and that, through sst1-3, the endothelial nitric oxide synthase (NOS) is inhibited [ 29 , 30 ].…”

“…SSAs exert their biological actions by binding to a family of G protein-coupled, seven transmembrane-spanning somatostatin receptors (sst1-sst5) in neuroendocrine cells, which, depending on the tumor type and the specific set of receptors involved, lead to decreased hormonal secretion, decreased growth and mitotic rates, increased apoptosis, and/or inhibition of cell signaling and protein synthesis, including inhibition of production and secretion of various angiogenic factors [ 8 – 11 ]. In mammals, ssts are encoded by five separate intronless genes (SSTR1-SSTR5), which have been classically considered to give rise to five different somatostatin receptors, named sst1 through sst5, plus, in mouse, a carboxyterminal spliced variant of sst2, named sst2B.…”

Evans Blue Attachment Enhances Somatostatin Receptor Subtype-2 Imaging and Radiotherapy

“…SST function is mediated specifically by five distinct subtypes of G-protein coupled receptors, namely somatostatin receptors 1-5 (SSTR1-5) 1 , 7 . These SSTRs are widely expressed in various tumors 8 , 9 .…”