【佳学基因靶向药物基因检测】六种一线酪氨酸激酶抑制剂揭示了 EGFR S768I 突变的新抑制潜力

基因品牌检测价格表2023年合理性

学习基因组组学个性化药物选择知悉《Toxicol Appl Pharmacol》在 2023 Jan 19;116385.发表了一篇题目为《》肿瘤靶向药物治疗基因检测临床研究文章。该研究由Ying Wang, Qian Liu, Chunhong Chu, Lanxin Li, Zhenxing Wang, Qiyu Liu, Guangyao Wu, Xiangkai Wei, Lei An, Jiguang Ma等完成。促进了肿瘤的精准治疗与个性化用药的发展，进一步强调了基因信息检测与分析的重要性。

肿瘤基因检测及靶向药物治疗研究关键词：

细胞毒性, EGFR S768I突变,肺腺癌,酪氨酸激酶抑制剂。

肿瘤治疗检测基因临床应用结果

肺癌是癌症相关死亡率的主要原因，也是最常被诊断出的癌症。酪氨酸激酶抑制剂 (TKI) 被认为是具有表皮生长因子受体 (EGFR) 突变的非小细胞肺癌 (NSCLC) 的药物靶向疗法。然而，关于 EGFR TKI 对罕见 EGFR 突变的活性的可用数据有限。在这里，基于 CRISPR 的内源性 EGFR 耗尽细胞系 H3255，使用细胞增殖测定、细胞毒性、膜电位、流式细胞术和蛋白质印迹分析测试了具有罕见突变体 EGFRS768I 和复合突变体 EGFRS768I+L858R 的 H3255 细胞。我们基于第一代、第二代和第三代 TKI（阿法替尼、达克替尼、奥希替尼、厄洛替尼、吉非替尼和埃克替尼）对六种一线 TKI 进行了 EGFR 突变的细胞毒性筛查。结果表明，这些含有罕见变体 EGFRS768I 的突变体对六种一线 TKI 的敏感性在不可逆 TKI 细胞毒性测定中通过确定它们在细胞毒性、细胞凋亡、细胞增殖和信号通路因子方面的变化而得到增强。重要的是，携带 EGFRL858R (H3255)、EGFRS768I (H3255S768I) 和 EGFRS768I+L858R (H3255S768I+L858R) 的变体对六种 TKI 敏感，并通过不同途径诱导细胞毒性。此外，复合突变 EGFRS768I+L858R 比 EGFRS768I 突变和 EGFRL858R 突变表现出更多的 TKI 耐药性。我们为 EGFRS768I 变体对六种一线 TKI 的敏感性提供了综合参考。对于具有 EGFR S768I 突变和复合突变 EGFRS768I+L858R 的患者，六种一线 TKI 似乎是合理的治疗选择。 EGFR S768I突变；肺腺癌；酪氨酸激酶抑制剂。

肿瘤发生与革命国际数据库描述：

Lung cancer, the leading cause of cancer-related mortality, is the most commonly diagnosed cancer. Tyrosine kinase inhibitors (TKIs) are considered a drug-targeted therapy for non-small cell lung cancers (NSCLCs) with epidermal growth factor receptor (EGFR) mutations. However, limited data are available involving the activity of EGFR TKIs against rare EGFR mutations. Here, based on an endogenous EGFR-depleted cell Line H3255 by CRISPR, H3255 cells with rare mutant EGFRS768I and compound mutations EGFRS768I+L858R were tested using cell proliferation assay, cytotoxicity, membrane potential, flow cytometry and Western blot analysis. We conducted cytotoxicity screening of EGFR mutations on six front-line TKIs based on first-, second-, and third-generation TKIs (afatinib, dacomitinib, osimertinib, erlotinib, gefitinib, and icotinib). The results showed that the sensitivity of these mutants containing rare variants EGFRS768I to six front-line TKIs was enriched in the irreversible TKI cytotoxicity assays by determining their change in cytotoxicity, apoptosis, cell proliferation and signal pathway factors. Importantly, the variants harboring EGFRL858R (H3255), EGFRS768I (H3255S768I) and EGFRS768I+L858R (H3255S768I+L858R) were sensitive to six TKIs and induced cytotoxicity through different pathways. Moreover, the compound mutations EGFRS768I+L858R showed more TKI resistance than EGFRS768I mutation and EGFRL858R mutation. We present a comprehensive reference for the sensitivity of EGFRS768I variants to six front-line TKIs. For patients with the EGFR S768I mutation and compound mutations EGFRS768I+L858R, six first-line TKIs appear to be reasonable therapeutic options.Keywords: Cytotoxicity; EGFR S768I mutation; Lung adenocarcinoma; Tyrosine kinase inhibitor.