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Kouroumalis et al. Hepatoma Res 2018;4:34 Hepatoma Research
DOI: 10.20517/2394-5079.2018.33

Review Open Access

Somatostatin in hepatocellular carcinoma:
experimental and therapeutic implications

Elias Kouroumalis , Demetrius Samonakis , George Notas 3
1,2
1
1 Department of Gastroenterology, University of Crete Medical School, Heraklion 71003, Greece.
2 Department of Gastroenterology, University Hospital, Heraklion 71100, Greece.
3 Department of Experimental Medicine, University of Crete Medical School, Heraklion 71003, Greece.
Correspondence to: Dr. Elias Kouroumalis, Department of Gastroenterology, University of Crete Medical School, Heraklion
71003, Greece. E-mail: kouroumi@uoc.gr
How to cite this article: Kouroumalis E, Samonakis D, Notas G. Somatostatin in hepatocellular carcinoma: experimental and
therapeutic implications. Hepatoma Res 2018;4:34. http://dx.doi.org/10.20517/2394-5079.2018.33
Received: 31 Mar 2018 First Decision: 28 May 2018 Revised: 19 Jun 2018 Accepted: 19 Jun 2018 Published: 11 Jul 2018

Science Editor: Guang-Wen Cao Copy Editor: Jun-Yao Li Production Editor: Cai-Hong Wang

Abstract
The neuropeptide somatostatin has been shown to control the secretion of several hormones and growth factors, but
also to inhibit the proliferation of several tumor cells. Hepatocellular carcinoma (HCC) is a leading cause of death all over
the world due to very limited treatment modalities. Early reports showed that somatostatin may influence HCC growth,
making somatostatin a potential therapeutic candidate. The introduction of somatostatin analogues with long half-lives
has made this prospect feasible. In this review, experimental data regarding the presence of somatostatin receptors and
their functional significance in HCC are presented. Potential mechanisms of direct anti-tumoral activity of somatostatin,
including effects on tumor cell proliferation and apoptosis, inhibition of various trophic factors and angiogenesis are also
reviewed, as well as indirect actions affecting liver fibrosis, inflammation and macrophage-associated innate immunity.
Data on the use of somatostatin analogues for the treatment of induced HCC in experimental animals are presented and
human studies of somatostatin treatment of advanced HCC are critically analyzed. Reasons and pitfalls for treatment
failures are identified and indications for the proper use of somatostatin, either alone or as an adjunct to other modalities
in future trials are proposed.

Keywords: Somatostatin analogues, hepatocellular carcinoma, somatostatin receptors, action mechanisms, treatment

INTRODUCTION
Hepatocellular carcinoma (HCC) is the fifth most common cancer among men and the seventh among
women, with approximately 600,000 annual deaths worldwide. It is the third cause of cancer-associated

© The Author(s) 2018. Open Access This article is licensed under a Creative Commons Attribution 4.0
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