Insulin-like growth factor receptor-1 as an anti-cancer target: blocking transformation and inducing apoptosis

Curr Cancer Drug Targets. 2002 Sep;2(3):191-207. doi: 10.2174/1568009023333863.


IGF-IR (Insulin-like growth factor receptor 1) is a tetrameric glycoprotein composed of two alpha and two beta subunits. The alpha subunit localizes extra-cellularly for ligand binding, whereas the beta subunit consists of transmembrane chains and a cytoplasmic tyrosine kinase domain for enzymatic activity. IGF-IR ligands, IGF-I and IGF-II, are mitogens and survival factors for many cancer cells. Binding of ligands to the IGF-IR initiates a cascade of events leading to activation of signal transduction pathways, mainly MAPK and PI-3K pathways, to stimulate proliferation/mitogenesis, to induce neoplastic transformation, to inhibit apoptosis, and to promote angiogenesis and metastasis. It has been shown that the presence of IGF-IR was required for transformation induced by many oncogenes and over-expression or constitutive activation of IGF-IR gave rise to transformed phenotypes. Significantly, over-expression of IGF-IR was observed in multiple human cancers including carcinomas of breast, lung, colon, and prostate. Patients with IGF-IR positive cancers had a worse prognosis in some cases. Furthermore, down-regulation or functional inactivation of IGF-IR sensitized tumor cells to apoptosis and reversed tumor cell phenotype. Thus, IGF-IR appears to be a promising cancer target. Indeed, a variety of approaches aimed at targeting IGF-IR have been utilized to prove the concept, or are being developed for potential anticancer therapies. These include targeting functional IGF-IR on cell surface, targeting ligand/receptor interaction, targeting receptor expression and functions, and targeting receptor kinase activity. Cancer patients could eventually benefit from the development of these specific IGF-IR antagonists.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Cell Transformation, Neoplastic / drug effects*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Receptor, IGF Type 1 / biosynthesis
  • Receptor, IGF Type 1 / drug effects*
  • Receptor, IGF Type 1 / genetics
  • Receptor, IGF Type 1 / physiology
  • Structure-Activity Relationship


  • Antineoplastic Agents
  • Receptor, IGF Type 1