Overcoming resistance to tyrosine kinase inhibitors: lessons learned from cancer cells treated with EGFR antagonists

Cell Cycle. 2009 Jan 1;8(1):18-22. doi: 10.4161/cc.8.1.7324. Epub 2009 Jan 30.


Tyrosine kinase inhibitors (TKIs) are effective anti-cancer therapies but resistance to these agents eventually develops. Several models of resistance to TKIs have been studied including resistance to EGFR inhibitors. Recent studies in EGFR-dependent A431 cells found upregulation of the IGF1R pathway as a mechanism to overcome blockade of EGFR. This was associated with amplification of IGF1R signaling and recovery of downstream PI3K-AKT activation. This work adds to a growing body of cell lines in culture that have provided insights into mechanisms of resistance that can be interrogated in primary tumors in patients. In this review, these model systems and their applicability to human cancers, as well as strategies to identify and overcome resistance to TKIs, are discussed.

Publication types

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

MeSH terms

  • Drug Resistance, Neoplasm / drug effects*
  • ErbB Receptors / antagonists & inhibitors*
  • Humans
  • Models, Biological
  • Neoplasms / enzymology*
  • Neoplasms / pathology*
  • Protein Kinase Inhibitors / pharmacology*
  • Receptor, ErbB-2 / antagonists & inhibitors


  • Protein Kinase Inhibitors
  • ErbB Receptors
  • Receptor, ErbB-2