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The Pathophysiological Consequences of Somatostatin Receptor Internalization and Resistance

Department of Internal Medicine, Erasmus Medical Center, 3015 GD Rotterdam, The Netherlands

Somatostatin receptors expressed on tumor cells form the rationale for somatostatin analog treatment of patients with somatostatin receptor-positive neuroendocrine tumors. Nevertheless, although somatostatin analogs effectively control hormonal hypersecretion by GH-secreting pituitary adenomas, islet cell tumors, and carcinoid tumors, significant differences are observed among patients with respect to the efficacy of treatment. This may be related to a differential expression of somatostatin receptor subtypes among tumors. In addition, the property of somatostatin receptor subtypes to undergo agonist-induced internalization has important consequences for visualizing, as well as for therapy, of receptor-postive tumors using radioisotope- or chemotherapeutic-compound-coupled somatostatin analogs. This review covers the pathophysiological role of somatostatin receptor subtypes in determining the efficacy of treatment of patients with somatostatin receptor-positive tumors using somatostatin analogs, as well as the preclinical and clinical consequences of agonist-induced receptor internalization for somatostatin receptor-targeted radio- and chemotherapy. Herein, the development and potential role of novel somatostatin analogs is discussed.

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