title: Therapeutic potential of growth factors and their antagonists.
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.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, UAE University, Al Ain, The Emirates.
authors.forename: A
authors.initials: A
authors.lastname: Garner
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004815:Epidermal Growth Factor / Q000032:analysis / Q000737:chemistry; D005767:Gastrointestinal Diseases / Q000188:drug therapy / Q000209:etiology; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy / Q000209:etiology; D006131:Growth Inhibitors / Q000502:physiology / Q000627:therapeutic use*; D006133:Growth Substances / Q000502:physiology / Q000627:therapeutic use*; D006801:Humans; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary
chemical_list: D006131:Growth Inhibitors; D006133:Growth Substances; D004815:Epidermal Growth Factor