Advances in research on EGFR-TKI resistance mechanism and therapeutic strategies in non-small cell lung cancer

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) are of great significance for the treatment of patients with non-small cell lung cancer.First-generation EGFR-TKI (such as gefitinib and erlotinib) or second-generation EGFR-TKI (such as afatinib and dacomitinib) are effective in the treatment of EGFR-mutant non-small cell lung cancer, especially EGFR exon 19 deletion or exon 21 L858R mutation.However, due to acquired resistance, almost all cases will relapse after 1 to 2 years.The most common resistance mutation is the EGFR T790M secondary mutation in exon 20.Osimertinib is a third-generation EGFR-TKI targeting T790M mutation and has been shown to be highly potent against EGFR-mutant lung cancer.However, the occurrence of acquired resistance to the C797S tertiary mutation of the third generation EGFR-TKI has been observed.This article reviews these resistance mechanisms and discuss strategies for coping with EGFR-TKI resistance. Key words: Carcinoma, non-small-cell lung; Receptor, epidermal growth factor; Drug resistance, neoplasm; Epidermal growth factor receptor tyrosine kinase inhibitor