Study of the parameters related to anticancer effect of somatostatin on hepatomas

Somatostatin (sst) is a hormone - regulatory peptide with multiple and diverse role in the central nervous system, the gastrointestinal tract and other peripheral tissues. SST has inhibitory actions on various secretory and growth processes. Its actions are implemented via G-protein bound receptor family. The receptors (sstr1-5) bound with high afinity with natural sst, whereas synthetic analogues (created to overcome the limitation of short half-life of the natural sst) bound mainly to sstr 2, 3, and 5. Somatostatin receptors’ expression in human tumours in vivo & in vitro, in non-tumoural tissues and in vessels, provided the ground for intense research and important applications in the diagnosis and treatment, most characteristically in neuroendocrine tumours. The identification of somatostatin receptors in the liver experimentally (sinusoidal cells, Kupffer cells), in chronic liver diseases and in hepatocellular carcinoma – HCC) together with the clear value of sst in the treatment of portal hypertension, gave the evidence for the use of sst in the treatment of HCC. HCC is an important neoplasm as it represents the third cause of death from cancer. Its incidence rises worldwide. The radical therapeutic options (liver transplantation, resection or radiofrequency ablation in small HCC) are possible for a minority of HCC patients as screening is far from ideal. Palliative treatments (radiofrequency ablation, transarterial chemoembolisation) can prolong life in selected patients. Nevertheless many people are not candidates for any of the abovementioned treatments. The experience from the experimental models, the identification of sstr in liver strctures and the success of somatostatin analogues in neuroendocrine tumours gave the evidence to treat inoperable HCC with these regimens and study the factors related to the response and the outcome. After the original randomised study of octreotide in HCC, we conducted an open prospective study of long acting somatostatin analogues (octreotide, lanreotide) in 32 patients with inoperable HCC. The study showed better survival in the study group versus historic controls (median 15 months vs. 8, p