Management of acquired resistance to epidermal growth factor receptor kinase inhibitors in patients with advanced non-small cell lung cancer

Cancer. 2014 Aug 1;120(15):2289-98. doi: 10.1002/cncr.28723. Epub 2014 Apr 17.


The widespread adoption of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors for the first-line treatment of patients with advanced EGFR-mutated non-small cell lung cancer has resulted in acquired tyrosine kinase inhibitor resistance becoming a ubiquitous clinical problem. The identification of specific mechanisms of acquired resistance has allowed a better understanding of the biology and natural history of resistant disease, but is only now starting to impact treatment decisions. Strategies for managing acquired resistance in patients with advanced non-small cell lung cancer are complex and must be adapted to the individual characteristics of each patient's cancer. Although combination chemotherapy is the presumed standard of care for most patients, prospective trial data are lacking, highlighting the importance of offering patients participation in clinical trials in this setting. Emerging data from trials of third-generation mutant-specific EGFR kinase inhibitors suggests particular promise with this class of agents.

Keywords: acquired resistance; epidermal growth factor receptor (EGFR); non-small cell lung cancer; targeted therapy.

Publication types

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

MeSH terms

  • Animals
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / enzymology
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Drug Resistance, Neoplasm
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / genetics
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / enzymology
  • Lung Neoplasms / genetics
  • Protein Kinase Inhibitors / pharmacology*


  • Protein Kinase Inhibitors
  • EGFR protein, human
  • ErbB Receptors