Cooperative Hedgehog-EGFR signaling

Front Biosci (Landmark Ed). 2012 Jan 1;17:90-9. doi: 10.2741/3917.

Abstract

It has been known for many years that cooperative interactions between oncogenes (e.g. RAS, MYC, BCL2) can fuel cancer growth (1-5), but the restricted druggability of many of those interacting cancer genes has hampered translation of combined targeting to medical cancer therapy. The identification and characterization of cooperative cancer signaling pathways amenable to medical therapy is therefore a crucial step towards the establishment of efficient targeted combination treatments urgently needed to improve cancer therapy. Here we review recent findings of our group and colleagues on the molecular mechanisms of cooperative Hedgehog/GLI and Epidermal Growth Factor Receptor (EGFR) signaling, two clinically relevant oncogenic pathways involved in the development of many human malignancies. We also discuss the possible implications of these findings for the design of a therapeutic regimen relying on combined targeting of key effectors of both pathways.

Publication types

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

MeSH terms

  • ErbB Receptors / physiology*
  • Hedgehog Proteins / physiology*
  • Humans
  • MAP Kinase Signaling System
  • Models, Biological
  • Neoplasms / drug therapy
  • Neoplasms / physiopathology
  • Signal Transduction
  • Transcription Factors / physiology
  • Zinc Finger Protein GLI1

Substances

  • GLI1 protein, human
  • Hedgehog Proteins
  • Transcription Factors
  • Zinc Finger Protein GLI1
  • ErbB Receptors