【佳學(xué)基因靶向藥物基因檢測】六種一線酪氨酸激酶抑制劑揭示了 EGFR S768I 突變的新抑制潛力

基因品牌檢測價格表2023年合理性

學(xué)習(xí)基因組組學(xué)個性化藥物選擇知悉《Toxicol Appl Pharmacol》在?2023 Jan 19;116385.發(fā)表了一篇題目為《》腫瘤靶向藥物治療基因檢測臨床研究文章。該研究由Ying Wang,?Qian Liu,?Chunhong Chu,?Lanxin Li,?Zhenxing Wang,?Qiyu Liu,?Guangyao Wu,?Xiangkai Wei,?Lei An,?Jiguang Ma等完成。促進(jìn)了腫瘤的正確治療與個性化用藥的發(fā)展，進(jìn)一步強(qiáng)調(diào)了基因信息檢測與分析的重要性。

腫瘤基因檢測及靶向藥物治療研究關(guān)鍵詞：

細(xì)胞毒性, EGFR S768I突變,肺腺癌,酪氨酸激酶抑制劑。

腫瘤治療檢測基因臨床應(yīng)用結(jié)果

肺癌是癌癥相關(guān)死亡率的主要原因，也是賊常被診斷出的癌癥。酪氨酸激酶抑制劑 (TKI) 被認(rèn)為是具有表皮生長因子受體 (EGFR) 突變的非小細(xì)胞肺癌 (NSCLC) 的藥物靶向療法。然而，關(guān)于 EGFR TKI 對罕見 EGFR 突變的活性的可用數(shù)據(jù)有限。在這里，基于 CRISPR 的內(nèi)源性 EGFR 耗盡細(xì)胞系 H3255，使用細(xì)胞增殖測定、細(xì)胞毒性、膜電位、流式細(xì)胞術(shù)和蛋白質(zhì)印跡分析測試了具有罕見突變體 EGFRS768I 和復(fù)合突變體 EGFRS768I+L858R 的 H3255 細(xì)胞。我們基于先進(jìn)代、第二代和第三代 TKI（阿法替尼、達(dá)克替尼、奧希替尼、厄洛替尼、吉非替尼和?？颂婺幔αN一線 TKI 進(jìn)行了 EGFR 突變的細(xì)胞毒性篩查。結(jié)果表明，這些含有罕見變體 EGFRS768I 的突變體對六種一線 TKI 的敏感性在不可逆 TKI 細(xì)胞毒性測定中通過確定它們在細(xì)胞毒性、細(xì)胞凋亡、細(xì)胞增殖和信號通路因子方面的變化而得到增強(qiáng)。重要的是，攜帶 EGFRL858R (H3255)、EGFRS768I (H3255S768I) 和 EGFRS768I+L858R (H3255S768I+L858R) 的變體對六種 TKI 敏感，并通過不同途徑誘導(dǎo)細(xì)胞毒性。此外，復(fù)合突變 EGFRS768I+L858R 比 EGFRS768I 突變和 EGFRL858R 突變表現(xiàn)出更多的 TKI 耐藥性。我們?yōu)?EGFRS768I 變體對六種一線 TKI 的敏感性提供了綜合參考。對于具有 EGFR S768I 突變和復(fù)合突變 EGFRS768I+L858R 的患者，六種一線 TKI 似乎是合理的治療選擇。 EGFR S768I突變；肺腺癌；酪氨酸激酶抑制劑。

腫瘤發(fā)生與革命國際數(shù)據(jù)庫描述：

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.