Abstract: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) targeted therapy has great advantages compared to conventional chemotherapies and has become the first-line treatment of EGFR sensitive mutations in patients with advanced non-small cell lung cancer. However, the development of acquired drug resistance is inevitable. EGFR T790M mutation is the main mechanism of the first and second generation EGFR-TKIs. The thirdgeneration EGFR-TKIs including AZD9291 and CO-1686 showed favorable treatment effect in clinical trials. However, resistance problems appeared soon. This review summarized the resistance mechanisms of the third-generation EGFRTKIs and the potential coping strategy.

Key words: Epidermal growth factor receptor, Non-small cell lung cancer, The third-generation epidermal growth factor receptor tyrosine kinase inhibitors, Resistance mechanism