背景与目的对于伴表皮生长因子受体（epidermal growth factor receptor, EGFR）敏感型突变的晚期非小细胞肺癌（non-small cell lung cancer, NSCLC）患者，小分子酪氨酸激酶抑制剂（tyrosine kinase inhibitor, TKI）的显著疗效众所周知。但对于晚期NSCLC伴EGFR-L861Q突变的患者，TKIs治疗是否敏感，治疗时机和治疗方案该如何选择，至今尚无确切的循证医学证据。本研究旨在通过分析EGFR-L861Q与敏感突变型EGFR-L858R及野生型EGFR蛋白质空间构象的差异，结合临床实例探讨晚期NSCLC伴EGFR-L861Q突变患者的最佳治疗方案。方法利用同源模建重建野生型EGFR、敏感突变型EGFR-L858R及突变型EGFR-L861Q蛋白质的空间构象，并分析这三种空间构象之间的差异。结果敏感突变型EGFR-L858R与野生型EGFR蛋白质的空间构象差异显著。突变型EGFR-L861Q与敏感突变型EGFR-L858R及野生型EGFR的蛋白质空间构象均不完全相同。在临床中，我们总结了1例晚期NSCLC伴EGFR-L861Q突变的患者，应用化疗作为一线治疗，当肿瘤不再缩小时，换用TKIs维持治疗，复查肺部计算机断层扫描（computed tomography, CT），肿瘤较前相比进一步缩小。结论通过对突变型EGFR-L861Q的蛋白质空间构象进行分析比对，结合临床实例，对于晚期NSCLC伴EGFR-L861Q突变的患者，一线化疗后达到疾病控制时，换用TKIs维持治疗，可能获得令人满意的临床疗效。%Background and objective hTe signiifcant effcacy of tyrosine kinase inhibitors (TKIs) has been ap-proved 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. hTis study aims to discuss the best treatment for advanced NSCLC patients with EG-FR-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. hTe differences among the three kinds of protein conformation were analyzed using homologous modeling technique. Results hTe structure of EGFR-L858R and wild-type EGFR exhibited notable distinctions. hTe 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 ifrst-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 hTe analysis of the protein conformation of EGFR-L861Q muta-tion 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 atfer ifrst-line chemotherapy.
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