Molecular predictors of EGFR-TKI sensitivity in advanced non-small cell lung cancer

Int J Med Sci. 2008 Jul 11;5(4):209-17. doi: 10.7150/ijms.5.209.

Abstract

The epidermal growth factor receptor (EGFR) is overexpressed in the majority of non-small cell lung cancers (NSCLC) and is a major target for new therapies. Specific EGFR tyrosine kinase inhibitors (TKIs) have been developed and used for the treatment of advanced NSCLC. The clinical response, however, varies dramatically among different patient cohorts. Females, East Asians, non-smokers, and patients with adenocarcinoma usually show higher response rates. Meanwhile, a number of biological factors are also associated with EGFR-TKIs responsiveness. In order to better understand the predictive value of these biomarkers and their significance in clinical application we prepared this brief review. Here we mainly focused on EGFR somatic mutations, MET amplification, K-ras mutations, EGFRvIII mutation, EGFR gene dosage and expression, HER2 gene dosage and expression, and Akt phosphorylation. We think EGFR somatic mutation probably is the most effective molecular predictor for EGFR-TKIs responsiveness and efficacy. Mutation screening test can provide the most direct and valuable guidance for clinicians to make decision on EGFR-TKIs therapy.

Keywords: EGFR; gene amplification; non-small cell lung cancer; somatic mutation; tyrosine kinase inhibitor.

Publication types

  • Review

MeSH terms

  • Biomarkers, Tumor / genetics
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / pathology
  • ErbB Receptors / antagonists & inhibitors*
  • ErbB Receptors / genetics
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology
  • Mutation
  • Protein Kinase Inhibitors / therapeutic use*
  • Treatment Outcome

Substances

  • Biomarkers, Tumor
  • Protein Kinase Inhibitors
  • ErbB Receptors