Alterations in Genes of the EGFR Signaling Pathway and Their Relationship to EGFR Tyrosine Kinase Inhibitor Sensitivity in Lung Cancer Cell Lines
2009

EGFR Pathway in Lung Cancer

Sample size: 77 publication 10 minutes Evidence: high

Author Information

Author(s): Gandhi Jeet, Zhang Jianling, Xie Yang, Soh Junichi, Shigematsu Hisayuki, Zhang Wei, Yamamoto Hiromasa, Peyton Michael, Girard Luc, Lockwood William W., Lam Wan L., Varella-Garcia Marileila, Minna John D., Gazdar Adi F.

Primary Institution: University of Texas Southwestern Medical Center at Dallas

Hypothesis

What is the relationship between mutations, copy number gains, and response to tyrosine kinase inhibitors in lung cancer cell lines?

Conclusion

The study confirms that both EGFR mutations and copy number gains are important factors in determining sensitivity to tyrosine kinase inhibitors in lung cancer.

Supporting Evidence

  • Mutations were found in 50.6% of the cell lines studied.
  • Copy number gains were present in 64.9% of the cell lines.
  • EGFR mutations were associated with increased sensitivity to gefitinib.
  • KRAS mutations were linked to resistance to gefitinib.
  • Multivariate analyses showed that EGFR mutations and copy number gains were independent factors related to gefitinib sensitivity.

Takeaway

This study looked at lung cancer cells to see how changes in certain genes affect how well they respond to cancer drugs. They found that changes in the EGFR gene are really important for how well the drugs work.

Methodology

The study analyzed mutations and copy number gains in lung cancer cell lines using sequencing, quantitative PCR, fluorescence in situ hybridization, and array comparative genomic hybridization.

Limitations

The study was limited to non-small cell lung cancer cell lines and may not fully represent the complexity of lung cancer in patients.

Participant Demographics

The study focused on non-small cell lung cancer cell lines, primarily adenocarcinomas.

Statistical Information

P-Value

0.0014

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1371/journal.pone.0004576

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