Research progress on resistance mechanism of EGFR-TKIs targeted therapy for non-small cell lung cancer / 中国医师杂志

ABSTRACT

Non-small cell lung cancer (NSCLC) is the histological subtype with highest proportion of lung cancer. Since the discovery of NSCLC driver gene mutations, the drug treatment of NSCLC had evolved from conventional chemotherapy to molecular targeted therapy. Epidermal growth factor receptor (EGFR) was one of the most important driver genes of NSCLC. Three generations of tyrosine kinase inhibitors (TKIs) targeting mutant EGFR had been developed and applied to the clinic, and EGFR-tKIs Targeted therapy had significantly improved the progression-free survival(PFS) and overall survival(OS) of patients with NSCLC. However, most NSCLC patients inevitably developed drug resistance within 10-18 months after receiving targeted therapy with EGFR-TKIs. Great progress had been made on the research of EGFR-TKIs resistance mechanism in recent years. This article intended to briefly review the resistance mechanism of EGFR-TKIs targeted therapy in terms of EGFR secondary mutation, signal bypass activation, cell lineage switching and tumor microenvironment, etc.