The pathophysiological consequences of somatostatin receptor internalization and resistance.
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-positive 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.
Hofland
Leo J
LJ
Department of Internal Medicine, Erasmus Medical Center, 3015 GD Rotterdam, The Netherlands. hofland@imw3.fgg.eur.nl
Lamberts
Steven W J
SW
D000818:Animals; D004351:Drug Resistance; D015870:Gene Expression; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000532:radiotherapy; D019275:Radiopharmaceuticals / Q000627:therapeutic use; D017481:Receptors, Somatostatin / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D013004:Somatostatin / Q000494:pharmacology; D013618:Tachyphylaxis
D019275:Radiopharmaceuticals; D017481:Receptors, Somatostatin; D013004:Somatostatin