The therapeutic potential of agents targeting the type I insulin-like growth factor receptor

Expert Opin Investig Drugs. 2004 Dec;13(12):1569-77. doi: 10.1517/13543784.13.12.1569.

Abstract

The type I insulin-like growth factor receptor (IGF-1R) is a receptor tyrosine kinase that mediates insulin-like growth factor I (IGF-1) and IGF-2 signalling. Increased expression levels and/or enhanced activity of IGF-1R have been observed in many types of cancer. It is well documented that IGF-1R plays important roles in the proliferation, transformation, motility and metastasis of cancer cells. Therefore, IGF-1R has surfaced as an attractive target for cancer therapy. There are several aspects of this receptor that need to be considered when thinking about inhibitory strategies. In this review, several points relevant to targeting IGF-1R will be discussed, including the signalling pathways downstream of the receptor, the potential role for the insulin receptor in regulating IGF action and multiple cancer phenotypes regulated by this receptor. In addition, there are several strategies that could be used to inhibit IGF action. Inhibition of receptor function by lowering protein expression, decreasing kinase activity by small-molecule inhibitors, disrupting receptor function by monoclonal antibody blockade and neutralising circulating ligand all represent potential therapeutic strategies. As these strategies move forward to clinical trial, several important considerations need to be incorporated into the clinical trial design.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Gene Expression / drug effects
  • Humans
  • Insulin-Like Growth Factor I / metabolism
  • Neoplasms / drug therapy
  • Receptor, IGF Type 1 / drug effects*
  • Receptor, IGF Type 1 / genetics
  • Receptor, IGF Type 1 / metabolism
  • Receptor, IGF Type 1 / physiology
  • Signal Transduction / drug effects*

Substances

  • Antineoplastic Agents
  • Insulin-Like Growth Factor I
  • Receptor, IGF Type 1