Mechanisms of action and resistance of somatostatin analogues for the treatment of hepatocellular carcinoma: a message not well taken.
Somatostatin (SST) acts as an inhibitory peptide of various secretory and proliferative processes. Apart from neuroendocrine tumors, where SST analogues have an established role, they have been tested in other tumors such as hepatocellular carcinoma (HCC) in the view of the fact that chemotherapy is not working. Several positive reports have been published. Approximately 40% of patients respond with improved survival and an impressive quality of life. A usual misunderstanding in trial designs is that, although SST is not a rescue drug, selection of patients is inappropriate, with mostly moribund patients being recruited. SST analogues do not seem to work in 60% of HCCs and this has been linked to the presence of SST receptors (SSTR) in the tumor, while several resistance mechanisms might be involved. Future management should engage more specific SST analogues targeted to a tumor with a known SSTR map. The use of somatostatin analogues as an adjunct therapy in combination with other treatment modalities should also be investigated.
Samonakis
Dimitrios N
DN
Department of Gastroenterology & Hepatology, University Hospital of Heraklion, Heraklion, Crete, Greece. dsamon@freemail.gr
Notas
George
G
Christodoulakis
Nikolaos
N
Kouroumalis
Elias A
EA
D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy*; D015282:Octreotide / Q000494:pharmacology / Q000627:therapeutic use; D010456:Peptides, Cyclic / Q000494:pharmacology / Q000627:therapeutic use; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
D000970:Antineoplastic Agents; D010456:Peptides, Cyclic; C060347:lanreotide; D013004:Somatostatin; D015282:Octreotide