Pasireotide (SOM230): development, mechanism of action and potential applications.
Pasireotide (SOM230) is a multi-receptor ligand somatostatin analogue with high binding affinity for somatostatin receptor subtypes sst(1,2,3) and sst(5). Pasireotide potently suppresses GH, IGF-I and ACTH secretion, indicating potential efficacy in acromegaly and Cushing's disease. The prolonged inhibition of hormone secretion by pasireotide in animal models and expression of multiple sst receptors in carcinoid tumors suggests that pasireotide may have clinical advantages over octreotide in patients with carcinoid tumors. Direct and indirect antitumor activity has been observed in vitro with pasireotide, including sst receptor-mediated apoptosis and antiangiogenesis, suggesting a possible role for pasireotide in antineoplastic therapy. In summary, preclinical evidence, as well as preliminary results from clinical studies suggests that pasireotide is a promising new treatment for patients with symptoms of metastatic carcinoid tumors refractory or resistant to octreotide, de novo or persistent acromegaly, and that pasireotide has the potential to be the first directed medical therapy for Cushing's disease.
Schmid
Herbert A
HA
Novartis Institutes for BioMedical Research, Oncology Research, Novartis Pharma AG, Basel, Switzerland. herbert.schmid@novartis.com
D000172:Acromegaly / Q000188:drug therapy; D000324:Adrenocorticotropic Hormone / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000737:chemistry / Q000627:therapeutic use; D002276:Carcinoid Tumor / Q000188:drug therapy / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D013006:Growth Hormone / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000037:antagonists & inhibitors / Q000378:metabolism; D015282:Octreotide / Q000627:therapeutic use; D047748:Pituitary ACTH Hypersecretion / Q000188:drug therapy; D017481:Receptors, Somatostatin / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000627:therapeutic use; D013329:Structure-Activity Relationship
D018931:Antineoplastic Agents, Hormonal; D017481:Receptors, Somatostatin; D013004:Somatostatin; D007334:Insulin-Like Growth Factor I; D000324:Adrenocorticotropic Hormone; D013006:Growth Hormone; C517782:pasireotide; D015282:Octreotide