Journal
ANNALS OF ONCOLOGY
Volume 17, Issue 12, Pages 1733-1742Publisher
OXFORD UNIV PRESS
DOI: 10.1093/annonc/mdl105
Keywords
angiogenesis; apoptosis; antitumor; receptor; refractory tumor; somatostatin analog
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Background: There is a need for novel antitumor agents that demonstrate efficacy in currently refractory tumors without adding to the toxicity of therapy. The somatostatin analogs, which have demonstrated antineoplastic activities in experimental tumor models, and good tolerability and safety profiles are attractive candidates. Materials and Methods: Data from preclinical studies provide evidence for direct and indirect mechanisms by which somatostatin analogs exert antitumor effects. Results: Direct antitumor activities, mediated through somatostatin receptors (sst(1)-sst(5)) expressed in tumor cells, include blockade of autocrine/paracrine growth-promoting hormone and growth factor production, inhibition of growth factor-mediated mitogenic signals and induction of apoptosis. Indirect antitumor effects include inhibition of growth-promoting hormone and growth factor secretion, and antiangiogenic actions. Many human tumors express more than one somatostatin receptor subtype, with sst(2) being predominant. Somatostatin analogs such as octreotide and lanreotide, which present a high affinity for sst(2), are in current clinical use to alleviate symptoms in patients with endocrine tumors, and radiolabeled somatostatin analogs have been developed for diagnosis and radiotherapy. Conclusions: While the rationale exists for the use of somatostatin analogs as antitumor agents, studies are ongoing to identify analogs with activity across the range of receptor subtypes to maximize the potential of such treatment.
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