[Targeting--a new way to identify unknown tumor markers in blood vessels]

Lakartidningen. 2005 Feb;102(8):551-2, 554-5.
[Article in Swedish]

Abstract

The expression of specific molecules on the surface of vascular endothelial cells in tumours might be a key to anticancer therapy with angiostatic drugs. A new method to find these molecules on tumour vessels, targeting, is presented here. Some of these tumour-specific molecules have been identified by means of so called phage libraries. They are gene-manipulated phages, where the surface is decorated with randomly generated short peptides. After intravenous injection a few of the peptides, expressed on the surface of the phage, attach to complementary structures on the endothelial cell, as a ligand attaches to its receptor. Through biopsies and immunohistochemistry the phage can be isolated and identified. The part of the DNA of the phage that codes for the peptide-sequence of importance is sequenced. This seeking for such vessel-addresses can in the future be used for diagnostic purposes and also for local tumour-treatment. It is envisioned that cytotoxic drugs can be coupled to peptides on nanoparticles and act locally, in order to minimize toxic systemic side effects.

Publication types

  • Review

MeSH terms

  • Angiogenesis Inhibitors / therapeutic use*
  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Biomarkers, Tumor / metabolism*
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / antagonists & inhibitors*
  • Drug Screening Assays, Antitumor / methods*
  • Endothelium, Vascular / metabolism*
  • Exenatide
  • Glucagon / administration & dosage
  • Glucagon / analogs & derivatives*
  • Glucagon / antagonists & inhibitors*
  • Glucagon / pharmacology
  • Glucagon / therapeutic use
  • Glucagon-Like Peptide 1
  • Glucagon-Like Peptide-1 Receptor
  • Humans
  • Liraglutide
  • Nanostructures
  • Neoplasms / blood supply
  • Neoplasms / drug therapy*
  • Neovascularization, Pathologic / drug therapy
  • Peptide Fragments / administration & dosage
  • Peptide Fragments / antagonists & inhibitors*
  • Peptide Fragments / pharmacology
  • Peptide Library
  • Peptides / therapeutic use
  • Protein Precursors / administration & dosage
  • Protein Precursors / antagonists & inhibitors*
  • Protein Precursors / pharmacology
  • Receptors, Glucagon / antagonists & inhibitors
  • Venoms / therapeutic use

Substances

  • Angiogenesis Inhibitors
  • Antineoplastic Agents
  • Biomarkers, Tumor
  • GLP1R protein, human
  • Glucagon-Like Peptide-1 Receptor
  • Peptide Fragments
  • Peptide Library
  • Peptides
  • Protein Precursors
  • Receptors, Glucagon
  • Venoms
  • Liraglutide
  • Glucagon-Like Peptide 1
  • Glucagon
  • Exenatide
  • DP IV-related protease, human
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases