Somatostatin receptor expression in hepatocellular carcinoma: prognostic and therapeutic considerations

Abstract

Sorafenib is the only systemic therapy to demonstrate a significant survival benefit over supportive care in robust randomised controlled trials for advanced hepatocellular carcinoma (HCC). In the context of an intense search for prognostic and predictive factors for response and efficacy of different systemic therapies (including sorafenib), a number of molecular targets have been identified, paving new avenues for potential therapeutic opportunities. Such molecular targets include somatostatin receptor (SSTR)-related alterations. In this review, we provide an overview of the various considerations relating to SSTRs as potentially novel prognostic and predictive biomarkers for HCC with special emphasis on the therapeutic potential of somatostatin analogues in HCC management.

Association Between Somatostatin Receptor Expression and Clinical Outcomes in Neuroendocrine Tumors

“…Several studies have evaluated the potential prognostic value of SSTR expression profiles in NET. 6–8,22 However, most have included a relatively small number of samples or examined a limited number of SSTR subtypes. Recently, one comparatively comprehensive study evaluated expression of SSTR1 to SSTR5, in 31 midgut and 55 pancreatic NETs.…”

“…5,9,10,21 Several prior studies have examined associations between expression of somatostatin receptors and prognosis, though most studies have focused primarily on SSTR2. 6–8,22 In a study evaluating 79 pancreatic NETs for expression of SSTR2, high expression of SSTR2 was associated with a favorable prognosis. 22 Other studies including a range of gastroenteropancreatic NET have similarly found that SSTR2 expression is associated with favorable outcomes.…”

Somatostatin receptors in resected hepatocellular carcinoma: status and correlation with markers of poor prognosis

“…Somatostatin and chemically designed analogues (SSAs), such as octreotide and lanreotide, have direct and indirect antitumour effects . These effects are mediated through G‐protein‐coupled somatostatin receptors (SSTR1–SSTR5).…”

“…9,[12][13][14][15][16][17][18][19] Somatostatin and chemically designed analogues (SSAs), such as octreotide and lanreotide, have direct and indirect antitumour effects. [20][21][22][23] These effects are mediated through G-protein-coupled somatostatin receptors (SSTR1-SSTR5). SSAs bind SSTR2 with high affinity, whereas they bind SSTR1, SSTR3 and SSTR5 with much lower affinity, and no binding has been demonstrated for SSTR4.…”

Systemic treatment for hepatocellular carcinoma: Still unmet expectations

“…More interesting data came in to light with clinical studies of Somatostatin and its long acting analogues for advanced HCC with very promising initial results[11,12], given the antiproliferative activity of the hormone and the positivity of HCC in somatostatin receptors in roughly 40% of the tumors[13]. Further publications have documented that somatostatin leads to apoptosis and has antineoplastic properties.…”