The significance of somatostatin analogues in the antiproliferative treatment of carcinomas.
Somatostatin is a cyclic tetradecapeptide hormone. It was initially isolated from bovine hypothalami. Somatostatin inhibits endocrine and exocrine secretion, as well as tumor cell growth, by binding to specific cell-surface receptors. Its potent inhibitory activity is limited, however, by its rapid enzymatic degradation and the consequently short plasma half-life. Octreotide is a short somatostatin analogue with increased duration of action compared with somatostatin. Preclinical studies have focused on the anticancer effects of octreotide and the related somatostatin analogues. In vitro, at nanomolar concentrations, these analogues inhibit the growth of tumor cells that express high-affinity somatostatin receptors. Accordingly, such analogues potently inhibit the growth of somatostatin receptor-positive tumors in various rodent models. The range of cancers susceptible to octreotide and related somatostatin analogues includes mammary, pancreatic, gastric, colorectal, prostate, thyroid, and lung carcinomas. Moreover, an indirect antiproliferative effect of somatostatin analogues is achievable in somatostatin receptor-negative tumors whose growth is driven by factors (e.g., gastrin, insulin-like growth factor-1) that become down-regulated by somatostatin. The clinical effect of somatostatin analogues in terms of tumor response in cancer patients is a subject of controversy, however. Most responses have been seen in patients with pancreatic cancers.
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Klinik und Poliklinik für Innere Medizin II (Onkologie, Hämatologie, Endokrinologie, Stoffwechselerkrankungen), Friedrich-Schiller-Universität Jena, Germany.
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D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology / Q000627:therapeutic use*; D002455:Cell Division / Q000187:drug effects; D002986:Clinical Trials as Topic; D006131:Growth Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
D018931:Antineoplastic Agents, Hormonal; D006131:Growth Inhibitors; D013004:Somatostatin