Therapeutic potential of growth factors and their antagonists

Yale J Biol Med. 1992 Nov-Dec;65(6):715-23; dscussion 737-40.

Abstract

This article describes studies with four peptides, epidermal growth factor (EGF), transforming growth factor alpha (TGF alpha), gastrin-releasing peptide/bombesin (GRP), and gastrin. The mitogenic and anti-secretory activities of EGF/TGF alpha appear to be mediated by a single class of high-affinity membrane receptors but may involve different signal transducing mechanisms. Biological activity of EGF resides in the N-terminal 42 amino acid fragment with the C-terminal undecapeptide determining binding affinity. A parenteral depot formulation of an EGF-related peptide or a small molecule agonist of the EGF receptor could have utility in treating various ulcerative disorders of the gut. Although antagonism of EGF (and thus TGF alpha) receptors and/or transducing mechanisms is frequently cited as a potential therapeutic approach to hyperproliferative diseases, blocking the action of TGF alpha, GRP, or gastrin with neutralizing antibodies or receptor antagonists did not influence the growth of a wide range of solid tumors in nude mice. These findings suggest that, unless tumor growth displays absolute dependency on one particular mitogen, antagonism of a specific growth factor is unlikely to have great effect in cancer therapy.

Publication types

  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Epidermal Growth Factor / analysis
  • Epidermal Growth Factor / chemistry
  • Gastrointestinal Diseases / drug therapy
  • Gastrointestinal Diseases / etiology
  • Gastrointestinal Neoplasms / drug therapy
  • Gastrointestinal Neoplasms / etiology
  • Growth Inhibitors / physiology
  • Growth Inhibitors / therapeutic use*
  • Growth Substances / physiology
  • Growth Substances / therapeutic use*
  • Humans
  • Molecular Sequence Data
  • Protein Structure, Secondary

Substances

  • Growth Inhibitors
  • Growth Substances
  • Epidermal Growth Factor