Functional activity of the multiligand analog SOM230 at human recombinant somatostatin receptor subtypes supports its usefulness in neuroendocrine tumors.
Functional gastroenteropancreatic tumors express all 5 somatostatin receptor subtypes (sst) in different quantities. Octreotide and lanreotide treat patients with these tumors by binding preferentially to sst2 and, to a lesser extent, to sst3 and sst5 receptors, thereby controlling prominent symptoms caused by hormone hypersecretion (diarrhea and flushing). Although symptoms initially improve in most patients, a loss of response occurs in about 50% during continuous treatment. The functional activity at sst receptors of SOM230, a new multiligand somatostatin analog, has been described and compared with that of somatostatin (SRIF-14) and octreotide. These data show that SOM230 is a full agonist with nanomolar potency at sst(1,2,3) and sst5 receptors. The multiligand activity profile of SOM230, together with its nondesensitizing inhibitory effect on growth hormone and insulin-like growth factor-I secretion in rats, may underlie its successful use in clinical trials and its potential for use in refractory patients with carcinoid tumors.
Novartis Institutes for Biomedical Research, Novartis Pharma AG, Oncology and Neuroscience Research, WSJ.386.425, Basel, Switzerland. herbert.schmid@pharma.novartis.com
Herbert A
HA
Schmid
Philippe
P
Schoeffter
D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D045744:Cell Line, Tumor; D005576:Colforsin / Q000494:pharmacology; D006224:Cricetinae; D003412:Cricetulus; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006801:Humans; D017599:Neuroectodermal Tumors / Q000188:drug therapy / Q000378:metabolism*; D015282:Octreotide / Q000627:therapeutic use; D017481:Receptors, Somatostatin / Q000145:classification / Q000187:drug effects / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000627:therapeutic use; D014162:Transfection / Q000379:methods
D018931:Antineoplastic Agents, Hormonal; D017481:Receptors, Somatostatin; D011994:Recombinant Proteins; D005576:Colforsin; D013004:Somatostatin; C517782:pasireotide; D000242:Cyclic AMP; D015282:Octreotide