However, resistance gradually emerged: only 10-19% of patients with advanced non-small cell carcinoma experienced a tumor response to gefitinib;109,110 after using first-generation EGFR TKIs for approximately 9–14 months, almost all tumors progressed again.111 Afterwards, studies revealed that the reduced sensitivity to gefitinib or erlotinib in NSCLC was linked to EGFR-specific activating mutations.112–116. Here, EGFR is linked to neoplasm.