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.
Schmid
Herbert A
HA
Novartis Institutes for Biomedical Research, Novartis Pharma AG, Oncology and Neuroscience Research, WSJ.386.425, Basel, Switzerland. herbert.schmid@pharma.novartis.com
Schoeffter
Philippe
P
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