Antiproliferative effects of somatostatin analogs in pituitary adenomas

Abstract

The antisecretory effects of somatostatin (SRIF) and its analogs are widely recognised and provide the basis for treatment of hormonal hypersecretion in pituitary adenomas, especially in the settings of acromegaly. Evidence for an antiproliferative effect of these compounds has also been provided. This review focuses on the mechanisms transducing the antiproliferative effects of SRIF and its analogs on pituitary adenomas, and on the clinical consequences on tumor volume of pharmacological treatment of pituitary adenomas with these drugs.

Somatostatin and Somatostatin Receptors

“…Over 90% of patients on SST-analogs show decreases in circulating GH levels, while approximately 70% of those achieve biochemical normalization. As previously mentioned, SST-analog therapy frequently results in tumor shrinkage in roughly 50% of patients (Lamberts et al 2002;Bevan 2005;Melmed et al 2005;Ferrante et al 2006;Zatelli et al 2006;Resmini et al 2007). It is known that GH secreting pituitary adenomas seldomundergodesensitization to treatment, as acromegalic patients rarely show any signs of tachyphylaxis despite years of SST-analog therapy.…”

“…It was noted that not only was treatment blocking hormone secretion but it was also causing variable tumor shrinkage through a distinct antiproliferative effect. The antiproliferative effects of SST was demonstrated in normal dividing cells such as intestinal mucosal cells, activated lymphocytes, inflammatory cells, as well as in experimental tumor models for example solid tumors of transplanted rat mammary carcinomas and finally cultured cells derived from both endocrine and epithelial tumors (pituitary, thyroid, breast, prostate, colon, pancreas, lung, and brain) (Patel 1999;Csaba and Dournaud 2001;Lamberts et al 2002;Moller et al 2003;Weckbecker et al 2003;Olias et al 2004;Zatelli et al 2006). The antiproliferative effects of SST on normal or transformed cells can be directed by cell growth arrest and/or apoptosis; several SSTR signaling pathways have been implicated (Fig.…”

Pasireotide, a multiple somatostatin receptor subtypes ligand, reduces cell viability in non-functioning pituitary adenomas by inhibiting vascular endothelial growth factor secretion

“…Previous evidence has shown that somatostatin (SRIF) and its analogs might exert antiproliferative effects on pituitary adenomas, by interacting with one or more of its five transmembrane G-protein-coupled receptors (SSTR1-5; Zatelli et al 2006b). In addition, overexpression of SSTR2 in human pancreatic cancer cells markedly reduced microvessel density and VEGF expression (Carrere et al 2005), suggesting that SSTR2-induced antiproliferative effects might be mediated by a reduction in VEGF secretion and action in a paracrine fashion.…”

Treatment of acromegaly in the era of personalized and predictive medicine

“…The quantification of tumour SSTRs for prediction of response to SSA is currently being considered as a part of the work‐up carried out after surgical failure. However, the expression of the different SSTRs shows a high variability among patients, with the highest being of SSTR2 and SSTR5, followed by lower expression of SSTR1 and SSTR3 and a frequent absence of SSTR4 expression . In an initial clinical/molecular analysis in a series of 83 somatotropinomas that were part of the translational network initiative in Spain, the Molecular Registry of Pituitary Adenomas (REMAH) of the Spanish Society of Endocrinology, a similar expression pattern was observed: SSTR2 was present at the highest levels followed by SSTR5>SSTR3>SSTR1 .…”