[Therapeutic biomarkers of EGFR-TKI].

Non-small cell lung cancer(NSCLC)patients with activating mutations of the epidermal growth factor receptor(EGFR)gene have shown a dramatic response to EGFR tyrosine kinase inhibitors(EGFR-TKI)such as gefitinib and erlotinib. EGFR activating mutations including exon 19 deletion and exon 21 L858R are recognized as markers ofthe sensitivity to EGFR-TKI therapy in NSCLC. However, the emergence of acquired resistance is virtually inevitable, thus limiting improvement in patient outcomes. Several acquired-resistance mechanisms and candidates, including exon 20 T790M secondary mutation, MET amplification, a high-level of HGF expression, PTEN downregulation, FAS-NF-κB pathway activation, epithelial-mesenchymal transition, and conversion to small cell lung cancer, have been identified. Understanding the mechanisms of acquired resistance to EGFR-TKI, followed by the development of molecular targeted drugs that can overcome the resistance, could serve as an important advance for targeting EGFR, which is activated in NSCLC. Further studies should be performed to clarify other mechanisms associated with the acquired resistance to EGFR-TKI. In this review, we summarize recent advances in the therapeutic biomarkers to EGFR-TKI.