Somatostatin Receptors in Non-Neuroendocrine Malignancies: The Potential Role of Somatostatin Analogs in Solid Tumors

Abstract

Somatostatin receptors (sstrs) are G-protein-coupled receptors that mediate various physiological effects when activated by the neuropeptide somatostatin or its synthetic analogs. In addition to the well-documented antisecretory effects of sstr(2)-preferential somatostatin analogs octreotide and lanreotide, ligand binding to sstr initiates an inhibitory action on tumor growth. This effect may result from both indirect actions (suppression of growth factors and growth-promoting hormones [e.g., GH/IGF-1 axis] and inhibition of angiogenesis) and direct actions (activation of antigrowth activities [e.g., apoptosis]). As solid tumor cells express multiple sstrs, there is a rationale to evaluate the potential antitumor effects of pasireotide (SOM230), a multireceptor-targeted somatostatin analog with high binding affinity for sstr(1-3) and sstr(5). Pasireotide reduces systemic IGF-1 levels more potently than currently available somatostatin analogs and has been well tolerated in clinical trials.

The GH-IGF-SST system in hepatocellular carcinoma: biological and molecular pathogenetic mechanisms and therapeutic targets

“…Changes in the expression pattern of GH-IGF axis have been reported in HCC, suggesting that this system plays a role in hepatocarcinogenesis [24]. Additionally, the activation of somatostatin receptors (SSTRs) may elicitate antitumoural effects through both direct (inhibition of cell proliferation and induction of apoptosis) and indirect (inhibition of cell proliferation and angiogenesis through the suppression of growth factors and growth-promoting hormones, such as GH and IGF1) mechanisms [25,26]. HCC has been reported to express SSTRs, although literature data about the antineoplastic effects of the somatostatin analogues (SA) in HCC are still controversial [27,28].…”

“…In a subset of patients with NET, SA have been found to improve clinical syndrome, to control hormonal secretion and to inhibit tumour growth [26,194,195]. Additionally, radiolabeled-SA have been developed and are clinically used to visualize NETs or to perform radiometabolic treatments in NET patients [25].…”

Craniopharyngioma cell growth is promoted by growth hormone (GH) and is inhibited by tamoxifen: Involvement of growth hormone receptor (GHR) and IGF-1 receptor (IGF-1R)

“…Most other GH-IGF-1 axis inhibitors are still in the experimental stage. 10 Among them, pegvisomant, a somatostatin analogue is commercially available to block excessive serum GH, and is used to treat solid tumors; 11,12 but their effect on CP cells is yet to be discovered. Somatostatin analogues act on their own receptors, and they may inhibit residual CP growth without compromising the somatotrophic effect of GH on normal tissues.…”

Association Between Insulin-like Growth Factor-2 Expression and Prognosis after Transcatheter Arterial Chemoembolization and Octreotide in Patients with Hepatocellar Carcinoma

“…As a result, it is the largest difficulty in the treatment. Somatostatin can combine with somatostatin receptor (SSTR) expressed by tumor cells and then inhibit promoting tumor growth hormone or cytokine's production and adjust tumor blood supply (Hasskarl et al, 2011;Jiang et al, 2011;Zhang et al, 2011;Laznicek et al, 2012;Niu et al, 2012). Insulin-like growth factor-2 (IGF-2) is an important angiogenic factor during the process which HCC induced neovascularization (El Tayebi et al, 2011;Rehem et al, 2011;Wachter et al, 2012 of HCC.…”