Functional activity of the multiligand analog SOM230 at human recombinant somatostatin receptor subtypes supports its usefulness in neuroendocrine tumors

Neuroendocrinology. 2004:80 Suppl 1:47-50. doi: 10.1159/000080741.

Abstract

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.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Antineoplastic Agents, Hormonal / therapeutic use
  • Cell Line, Tumor
  • Colforsin / pharmacology
  • Cricetinae
  • Cricetulus
  • Cyclic AMP / metabolism
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Humans
  • Neuroectodermal Tumors / drug therapy
  • Neuroectodermal Tumors / metabolism*
  • Octreotide / therapeutic use
  • Receptors, Somatostatin / classification
  • Receptors, Somatostatin / drug effects
  • Receptors, Somatostatin / metabolism*
  • Recombinant Proteins / metabolism
  • Somatostatin / analogs & derivatives*
  • Somatostatin / pharmacology*
  • Somatostatin / therapeutic use
  • Transfection / methods

Substances

  • Antineoplastic Agents, Hormonal
  • Receptors, Somatostatin
  • Recombinant Proteins
  • Colforsin
  • Somatostatin
  • pasireotide
  • Cyclic AMP
  • Octreotide