Study backgroud: third generation of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is the newest target therapy for non small cell lung cancer (NSCLC). Two major study published in NEJM show that the overall response rate is about 60%-70%, with a progression free survival about 10 months. However, we did not known the specific mechanisms for those non-responders and patients grow resistance.