The insulin-like growth factor (IGF) axis as an anticancer target in prostate cancer

Cancer Lett. 2015 Oct 28;367(2):113-21. doi: 10.1016/j.canlet.2015.07.026. Epub 2015 Jul 29.

Abstract

Prostate cancer (PCa) is the most common cancer and the second leading cause of cancer death in males. In recent years, several new targeting agents have been introduced for the treatment of advanced stages of the disease. However, development of resistance limits the efficacy of new drugs and there is a further need to develop additional novel treatment approaches. One of the most investigated targets in cancer research is the insulin-like growth factor (IGF) axis, whose receptors are overexpressed in several cancer entities including PCa. In preclinical studies in PCa, targeting of the IGF axis receptors showed promising anti-tumor effects. Currently available data on clinical studies do not meet the expectations for this new treatment approach. In this review we provide a summary of preclinical and clinical studies on the IGF axis in PCa including treatment with monoclonal antibodies and tyrosine kinase inhibitors. Moreover, we summarize preliminary results from ongoing studies and discuss limitations and side effects of the substances used. We also address the role of the IGF axis in the biomarkers setting including IGF-binding proteins and genetic variants.

Keywords: Biomarker; IGF targeting therapies; Insulin receptor; Insulin-like growth factor receptor-1; Prostate cancer.

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Monoclonal / therapeutic use
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Biomarkers, Tumor / antagonists & inhibitors*
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Drug Design*
  • Genetic Variation
  • Humans
  • Insulin-Like Growth Factor I / antagonists & inhibitors*
  • Insulin-Like Growth Factor I / genetics
  • Insulin-Like Growth Factor I / metabolism
  • Male
  • Molecular Targeted Therapy*
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology
  • Protein Kinase Inhibitors / therapeutic use
  • Receptor, IGF Type 1 / antagonists & inhibitors*
  • Receptor, IGF Type 1 / genetics
  • Receptor, IGF Type 1 / metabolism
  • Signal Transduction / drug effects*
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Protein Kinase Inhibitors
  • Insulin-Like Growth Factor I
  • Receptor, IGF Type 1