This study is based on the following hypothesis "De novo resistance to EGFR-TKI in EGFR mutation positive patients is related with mutations in EGFR downstream genes".

Investigators will prospectively collect genomic DNA and clinical data regarding treatment outcomes to EGFR-TKI in NSCLC patients with activating EGFR mutations. Investigators will sequence candidate mutations of EGFR downstream genes and analyze c-met gene amplification and protein expression in PTEN, HGF, and IGFR. To identify genetic mutations, amplification, and protein over expression as predictive markers of treatment outcomes, investigators analyzed the association of treatment outcomes with the presence of genetic alteration or protein over expression. Investigators will attempt to identify biomarkers that are able to predict de novo resistance to EGFR-TKI in EGFR mutated NSCLC.

Investigators will prospectively enroll patients who match the following criteria: pathologically proven unresectable NSCLC, planning to treat with EGFR-TKI, patients with activating EGFR mutations, and available tissue sample for DNA extraction.

Inclusion Criteria:

1. Pathologically proven unresectable NSCLC
2. 20 years of age or older
3. Planned treatment with Iressa®
4. Patients with activating EGFR mutation (del 19, L858R)
5. Available detailed smoking history
6. Available tissue samples (archival tissue) for mutational or molecular analysis (representative paraffin block or unstained sections from tumor diagnostic specimen are mandatory)
7. Available blood sample
8. At least one lesion that is measurable according to the RECIST 1.1 criteria by CT or MRI
9. Written informed consent

Exclusion Criteria:

1. More than 3rd line treatment
2. Previously treated with other EGFR-TKI
3. Life expectancy of less than 12 weeks
4. Pregnant or lactating female
5. Any unresolved toxicity greater than CTC grade 2 (version 4.0) from previous anti cancer treatment.
6. Unsuitable patient in this treatment as determined by doctor.

NSCLC patient with EGFR mutation