EGFR-L861Q突变对TKI类药物敏感性预测分析及病例报道

BACKGROUND AND OBJECTIVE: The significant efficacy of tyrosine kinase inhibitors (TKIs) has been approved for advanced non-small cell lung cancer (NSCLC) patients with activating epidermal growth factor receptor (EGFR) mutations. No clear evidence exists that EGFR-L861Q is sensitive to TKIs, and the best treatment for NSCLC patients with EGFR-L861Q mutation is undetermined. This study aims to discuss the best treatment for advanced NSCLC patients with EGFR-L861Q mutation by analyzing the differences among the structures of wild-type EGFR, activating mutant EGFR-L858R, and EGFR-L861Q mutation. METHOD: The protein structures of wild-type EGFR were reconstructed. EGFR-L858R and EGFR-L861Q mutation were activated. The differences among the three kinds of protein conformation were analyzed using homologous modeling technique. RESULTS: The structure of EGFR-L858R and wild-type EGFR exhibited notable distinctions. The structure of EGFR-L861Q mutation was different compared with wild-type EGFR and activating mutant EGFR-L858R protein conformations. NSCLC patients with EGFR-L861Q mutation were given chemotherapy as the first-line of therapy, and TKIs were applied to maintain treatment when the tumor is unchanged. Effect evaluation result was improved when the lung computed tomography lesions were reviewed. CONCLUSION: The analysis of the protein conformation of EGFR-L861Q mutation and the curative effect of chemotherapy with TKIs could help predict the sensitivity of EGFR-L861Q to TKIs. Combining the analysis with a clinical case, maintenance treatment with TKIs may achieve satisfactory curative effect in advanced NSCLC patients who have achieved disease control after first-line chemotherapy.