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International Journal of Clinical Oncology

, Volume 11, Issue 3, pp 190–198 | Cite as

Biological and clinical implications of EGFR mutations in lung cancer

  • Tetsuya MitsudomiEmail author
  • Takayuki Kosaka
  • Yasushi Yatabe
REVIEW ARTICLE

Abstract

Background

Patients with non-small-cell lung cancer sometimes show a dramatic clinical response to gefitinib or erlotinib, small-molecule tyrosine kinase inhibitors (TKI) specific for the epidermal growth factor receptor (EGFR). However, until April 2004, it was unclear how to identify patients who would benefit from these drugs. Then, two groups from Boston reported that EGFR gene mutations in the kinase domain are strongly associated with gefitinib sensitivity. EGFR mutations are more frequent in Asians, females, nonsmokers, and adenocarcinomas than in their counterparts. These populations precisely coincide with those populations with higher response rates to TKIs. We and others subsequently confirmed and extended these findings.

Methods

We reviewed recent literatures on EGFR mutations and EGFR-TKIs. We discuss topics including the molecular epidemiology and biology of EGFR mutations in relation to EGFR-TKIs, the controversy about whether EGFR mutations account for all the clinical activity of EGFR-TKIs, and the mechanisms of acquired resistance to gefitinib or erlotinib.

Results

The discovery of EGFR mutations has great biologic and clinical implications in lung cancer. However, all but one phase III trials have so far failed to show a survival advantage of the treatment arm involving EGFR-TKIs.

Conclusion

It would be possible to individualize EGFR-TKI treatment of lung cancer by selecting patients according to EGFR mutational status and other biomarkers.

Key words

Molecular targeted therapy Tyrosine kinase inhibitor Gefitinib Individualized therapy Predictive factor 

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Copyright information

© The Japan Society of Clinical Oncology 2006

Authors and Affiliations

  • Tetsuya Mitsudomi
    • 1
    Email author
  • Takayuki Kosaka
    • 1
  • Yasushi Yatabe
    • 1
  1. 1.Department of Thoracic Surgery and Department of Pathology and Molecular DiagnosticsAichi Cancer Center Hospital, Aichi Cancer CenterNagoyaJapan

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