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Pasireotide (SOM230) as a Potential Treatment for Endocrine and Non- Endocrine Tumors

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Neuroendocrine tumors are usually characterized by the overexpression of somatostatin receptors, the presence of secretory granules and the ability to secrete amines or hormones. Somatostatin receptor expression profiles vary by tumor type and may even vary over the course of the disease. Furthermore, multiple somatostatin receptor subtypes are also expressed in a number of non-neuroendocrine tumors.

Pasireotide is a multi-receptor targeted somatostatin analogue with high binding affinity for four of the five somatostatin receptor subtypes sst1,2,3 and sst5. Prolonged inhibition of hormone secretion by pasireotide in animal models and expression of multiple somatostatin receptors in neuroendocrine tumors suggest that pasireotide may have clinical advantages over the sst2-preferential somatostatin analogues, octreotide and lanreotide. Clinical trials demonstrated pasireotide to be a promising treatment for patients with acromegaly, Cushing's disease and GI-NETs, and results from ongoing Phase III clinical studies will determine the role of pasireotide in these indications.

Somatostatin analogues may have direct antitumor effects through receptor-mediated signal transduction pathways and indirect antitumor effects via inhibition of angiogenesis, suppression of growth factors and growth-promoting hormone synthesis/secretion or immunomodulatory effects. As such, pasireotide is under preclinical and clinical investigation as an antiproliferative therapy in several malignancies, both endocrine and non-endocrine.

Keywords: Acromegaly; Cushing's disease; G-protein; Gastroenteropancreatic; Neuroendocrine tumors; Pasireotide; adrenocorticotrophin hormone; alcitonin; analogue; androgen- independent growth; antiproliferative; antisecretory effect; bleomycin; bronchoalveolar; carcinoid syndrome; corticosteroids; corticotroph tumor cells; cynomologus; dexamethasone treatment; endocrine islets; gastrinomas; gonadotroph adenomas; hormones; hypopituitarism; insulinomas; lanreotide; malignancies; neuroendocrine tumor; octreotide; oncological disorders; pituitary adenoma; prolactin; prolactinomas; solid tumor; somatostatin; somatostatin analogue; somatostatin receptors; sst; sst5 regulates; tamoxifen; transsphenoidal surgery

Document Type: Research Article

Publication date: November 1, 2010

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