阿美替尼和阿法替尼对罕见的 EGFR S768I 突变细胞表现出新颖的抑制作用。
Almonertinib and alflutinib show novel inhibition on rare EGFR S768I mutant cells.
机构信息
Department of Anesthesiology, The First Affiliated Hospital of Henan University, Henan University, No. 357, Ximen Avenue, Kaifeng, 475000, Henan, China.
Translational Medicine Center, Huaihe Hospital of Henan University, Henan University, No. 115, Ximen Avenue, Kaifeng, 475000, China.
出版信息
Clin Transl Oncol. 2024 Dec;26(12):3100-3115. doi: 10.1007/s12094-024-03494-5. Epub 2024 May 30.
PURPOSE
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.
METHODS
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.
RESULTS
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.
CONCLUSIONS
These findings suggest that almonertinib and alflutinib may be potential therapeutic options for non-small cell lung cancer patients with the EGFR S768I mutation.
目的
EGFR 经典突变对 EGFR 酪氨酸激酶抑制剂反应良好。然而，目前尚不确定现有的 EGFR-TKIs 是否对罕见的 EGFR 突变和复合突变有效。在此，鉴定了中国开发的第三代酪氨酸激酶抑制剂阿美替尼和阿来替尼对罕见 EGFR S768I 突变和复合突变的疗效。
方法
本研究采用 CRISPR 方法构建了 4 种 EGFR S768I 突变细胞系，并测试了 EGFR 对阿美替尼和阿来替尼的敏感性，阳性对照为第 1 （吉非替尼）、第 2 （阿法替尼）和第 3 （奥希替尼）代药物。
结果
本研究结果表明，阿美替尼和阿来替尼通过阻断细胞周期和抑制细胞凋亡，通过 ERK 或 AKT 通路，以时间依赖的方式有效抑制罕见的 EGFR S768I 突变细胞的活力和增殖。
结论
这些发现表明，阿美替尼和阿来替尼可能是具有 EGFR S768I 突变的非小细胞肺癌患者的潜在治疗选择。
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