The type I insulin-like growth factor receptor pathway: a key player in cancer therapeutic resistance

Front Biosci. 2008 May 1;13:3273-87. doi: 10.2741/2925.

Abstract

The insulin-like growth factor (IGF) ligands stimulate cellular proliferation and survival by activating the type I insulin-like growth factor receptor (IGF-IR). As a result, the IGF signaling system is implicated in a number of cancers, including those of the breast, prostate, and lung. In addition to mitogenic and anti-apoptotic roles that may directly influence tumor development, IGF-IR also appears to be a critical determinant of response to numerous cancer therapies. This review describes the role of the IGF-IR pathway in mediating resistance to both general cytotoxic therapies, such as radiation and chemotherapy, and targeted therapies, such as tamoxifen and trastuzumab. It concludes with a description of approaches to target IGF-IR and argues that inhibition of IGF signaling, in conjunction with standard therapies, may enhance the response of cancer cells to multiple modalities.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Breast Neoplasms / therapy
  • Drug Resistance, Neoplasm*
  • Estradiol / analogs & derivatives
  • Estradiol / therapeutic use
  • Female
  • Fulvestrant
  • Humans
  • Male
  • Neoplasms / drug therapy*
  • Neoplasms / radiotherapy*
  • Prostatic Neoplasms / therapy
  • Raloxifene Hydrochloride / therapeutic use
  • Receptor, IGF Type 1 / physiology*
  • Selective Estrogen Receptor Modulators / therapeutic use
  • Signal Transduction
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Selective Estrogen Receptor Modulators
  • Fulvestrant
  • Raloxifene Hydrochloride
  • Estradiol
  • Receptor, IGF Type 1