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CLIN CANCER RES：非小细胞肺癌患者Osimertinib耐药机制

2018-07-05 MedSci MedSci原创

非小细胞肺癌osimertinib耐药机制
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三代EGFR酪氨酸激酶抑制剂Osimertinib主要用于治疗一代及二代耐药的EGFR T790阳性非小细胞肺癌患者。获得性EGFR C797S突变被认为在某些患者中可以调节Osimertinib耐药。但是其耐药机制尚不清楚。CLIN CANCER RES近期发表了一篇文章研究这一问题。

三代EGFR酪氨酸激酶抑制剂Osimertinib主要用于治疗一代及二代耐药的EGFR T790阳性非小细胞肺癌患者。获得性EGFR C797S突变被认为在某些患者中可以调节Osimertinib耐药。但是其耐药机制尚不清楚。CLIN CANCER RES近期发表了一篇文章研究这一问题。

作者利用靶向二代测序技术检测了93例Osimertinib耐药肺癌患者样本的416个肿瘤相关基因，主要样本为循环DNA（cfDNA），并与12例治疗前患者标本进行匹配。通过体内实验验证鉴别出的继发EGFR突变功能。研究结果表明，分别在24.7%，10.8%和9.7%的标本中发现了EGFR G796/C797，L792和L718/G719突变。L798和L718在Osimertinib半数抑制浓度时显着增加，L718Q对Osimertinib最显着耐药有重要作用。12对配对的治疗前样本分析表明在Osimertinib治疗期间出现了EGFR突变。研究还发现了突变下游基因如MET，KRAS和PIK3CA，可能有助于无EGFR继发突变的患者出现Osimertinib耐药。

文章最后认为，该研究使用cfDNA检测了Osimertinib耐药的肺癌患者的突变情况。处了C797突变，EGFR L718和L792等继发突变有利于Osimertinib耐药，具有重要的临床和药理学意义。

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    2018-11-29 lingaifan

    #非小细胞#

    0

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    2019-02-01 zhaojie88

    #耐药机制#

    0

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    2018-12-27 gds2009

    #肺癌患者#

    0

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    2018-07-07 dongjia2012

    #osimertinib#

    0

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    2018-07-07 zxxiang

    #非小细胞肺癌患者#

    0

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