Which biomarker predicts benefit from EGFR-TKI treatment for patients with lung cancer?

Br J Cancer. 2007 Mar 26;96(6):857-63. doi: 10.1038/sj.bjc.6603665. Epub 2007 Feb 27.


Subsets of patients with non-small cell lung cancer respond remarkably well to small molecule tyrosine kinase inhibitors (TKI) specific for epidermal growth factor receptor (EGFR) such as gefitinib or erlotinib. In 2004, it was found that EGFR mutations occurring in the kinase domain are strongly associated with EGFR-TKI sensitivity. However, subsequent studies revealed that this relationship was not perfect and various predictive markers have been reported. These include EGFR gene copy numbers, status of ligands for EGFR, changes in other HER family genes or molecules downstream to EGFR including KRAS or AKT. In this review, we would like to review current knowledge of predictive factors for EGFR-TKI. As all but one phase III trials failed to show a survival advantage of the treatment arm involving EGFR-TKIs, it is necessary to select patients by these biomarkers in future clinical trials. Through these efforts, it would be possible to individualise EGFR-TKI treatment for patients suffering from lung cancer.

Publication types

  • Clinical Trial, Phase III
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Biomarkers, Tumor / biosynthesis*
  • Biomarkers, Tumor / genetics
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / enzymology
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Drug Delivery Systems
  • ErbB Receptors / antagonists & inhibitors*
  • ErbB Receptors / biosynthesis
  • ErbB Receptors / genetics
  • Genes, erbB-1
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / enzymology*
  • Lung Neoplasms / genetics
  • Mutation
  • Predictive Value of Tests
  • Protein Kinase Inhibitors / therapeutic use*


  • Biomarkers, Tumor
  • Protein Kinase Inhibitors
  • ErbB Receptors