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当代肿瘤药物靶点

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ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

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Research Article

软脑膜内膜转移瘤非小细胞肺癌患者脑脊液和血浆的Osimertinib定量和基因变异分析

卷 19, 期 8, 2019

页: [666 - 673] 页: 8

弟呕挨: 10.2174/1568009618666181017114111

价格: $65

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摘要

背景：软脑膜转移瘤（LM）在携带表皮生长因子受体（EGFR）突变的非小细胞肺癌（NSCLC）患者中更为频繁。 Osimertinib是第三代表皮生长因子受体酪氨酸激酶抑制剂（EGFRTKI），对LM有很好的疗效。 目的：本研究旨在分析人血浆和脑脊液（CSF）中osimertinib的浓度和循环肿瘤DNA（ctDNA）的基因变异。 此外，我们探讨了CSF中的ctDNA是否可以用作预测和监测治疗反应的生物标志物。 方法：从患有LM获得性EGFR-TKI抗性的NSCLC患者中收集动态配对CSF和血液样品。 开发了一种基于超高效液相色谱 - 串联质谱（UPLC-MS / MS）的方法，用于检测CSF和血浆样品中的osimertinib。 通过使用一组1021个基因的新一代测序来测试ctDNA的基因变异。 结果：脑脊液中奥司他替的浓度显着低于血浆（渗透率为1.47％）。 在来自血浆和CSF样品的ctDNA中研究了突变，包括mTOR，EGFR，CHECK1，ABCC11和TP53。 检测到的CSF样本突变率高于血浆样本（50％对25％）。 我们的数据进一步揭示了源自CSF的ctDNA的变异等位基因频率（VAF）和分子肿瘤负荷指数（mTBI）与治疗效果呈负相关。 结论：来自CSF的ctDNA可能是监测治疗效果的有用生物标志物，也是LM核磁共振成像（MRI）的有效补充。

关键词: 软脑膜转移瘤，非小细胞肺癌，Osimertinib，UPLC-MS / MS，新一代测序，脑脊液，血浆

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