EGFR 经典突变对 EGFR 酪氨酸激酶抑制剂反应良好。然而，目前可用的EGFR-TKIs是否对罕见EGFR突变和复合突变有效尚不确定。在此，鉴定了我国开发的第三代酪氨酸激酶抑制剂阿莫替尼和阿氟替尼对罕见EGFR S768I突变和复合突变的有效性。本研究利用CRISPR方法构建了4个EGFR S768I突变细胞系，并通过测试了 EGFR 对 almonertinib 和 alflutinib 的敏感性，阳性对照为第一代（吉非替尼）、第二代（阿法替尼）和第三代（奥希替尼）药物。目前的结果表明，almonertinib 和 alflutinib 可以有效抑制罕见细胞中的细胞活力和增殖。 EGFR S768I 突变以时间依赖性方式通过 ERK 或 AKT 途径，阻断细胞周期并抑制细胞凋亡。这些研究结果表明，阿莫替尼和阿氟替尼可能是具有 EGFR S768I 突变的非小细胞肺癌患者的潜在治疗选择.© 2024。作者获得 Federación de Sociedades Españolas de Oncología (FESEO) 的独家许可。

EGFR classical mutations respond well to EGFR tyrosine kinase inhibitors. However, it is uncertain whether currently available EGFR-TKIs are effective against rare EGFR mutations and compound mutations. Herein, the effectiveness of almonertinib and alflutinib, the third-generation tyrosine kinase inhibitors developed in China, on rare EGFR S768I mutations and compound mutations is identified.In this study, using CRISPR method, four EGFR S768I mutation cell lines were constructed, and the sensitivity of EGFR to almonertinib and alflutinib was tested, with positive controls being the 1st (gefitinib), 2nd (afatinib), and 3rd (osimertinib) generation drugs.The present results indicate that almonertinib and alflutinib can effectively inhibit cell viability and proliferation in rare EGFR S768I mutations through the ERK or AKT pathways in a time-dependent manner, by blocking the cell cycle and inhibiting apoptosis.These findings suggest that almonertinib and alflutinib may be potential therapeutic options for non-small cell lung cancer patients with the EGFR S768I mutation.© 2024. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).