Studies of the Synergistic Effects of Raf-1 and Somotostatin Analogs on Carcinoids
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Somatostatin inhibits the release of various hormones through five somatostatin receptor subtypes. Somatostatin analogs have been used to treat patients with carcinoid disease to control the hormone release and tumor growth. Although, somatostatin analogs are effective therapy for this syndrome, patients often become resistant to somatostatin and are left with no palliative option for symptomatic control of the carcinoid syndrome. Therefore, there is a great need to develop novel therapeutic strategies both to reduce tumor burden as well as to control symptoms in patients with carcinoid neoplasms. We and others have previously reported that Raf-1 activation in MTC results in growth suppression as well as reduction in neuroendocrine hormones (such as calcitonin and serotonin), and human acheate-scute complex Like-1 (ASCL1) (Park et al 2003a; Sippel et al 2003a). Further, in human carcinoid tumor cells, there is significant reduction in levels of NE hormones with Raf-1 activation (Sippel et al 2003c; Sippel and Chen2002b). These results suggest that Raf-1 activation may be a possible therapeutic target in certain cancers such as neuroendocrine tumors. Therefore, we hypothesize that combination of therapy such as raf-1 activation and somatostatin analog might synergistically reduce tumor burden and hormone production.
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First published: 07/15/02 Last updated: 11/23/09 webmaster@surgery.wisc.edu
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