Functional selectivity of EGF family peptide growth factors: implications for cancer

Pharmacol Ther. 2009 Apr;122(1):1-8. doi: 10.1016/j.pharmthera.2008.11.008. Epub 2008 Dec 16.


Breast, prostate, pancreatic, colorectal, lung, and head and neck cancers exploit deregulated signaling by ErbB family receptors and their ligands, EGF family peptide growth factors. EGF family members that bind the same receptor are able to stimulate divergent biological responses both in cell culture and in vivo. This is analogous to the functional selectivity exhibited by ligands for G-protein coupled receptors. Here we review this literature and propose that this functional selectivity of EGF family members is due to distinctions in the conformation of the liganded receptor and subsequent differences in the sites of receptor tyrosine phosphorylation and receptor coupling to signaling effectors. We also discuss the roles of divergent ligand activity in establishing and maintaining malignant phenotypes. Finally, we discuss the potential of mutant EGF family ligands as cancer chemotherapeutics targeted to ErbB receptors.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antineoplastic Agents / pharmacology
  • Drug Delivery Systems
  • Epidermal Growth Factor / metabolism*
  • ErbB Receptors / metabolism*
  • Humans
  • Ligands
  • Neoplasms / drug therapy
  • Neoplasms / physiopathology*
  • Signal Transduction


  • Antineoplastic Agents
  • Ligands
  • Epidermal Growth Factor
  • ErbB Receptors