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Sci transl med：DHODH，可作为治疗小细胞肺癌的特异性靶点

2019-11-08 不详 MedSci原创

DHODH小细胞肺癌靶点
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小细胞肺癌（SCLC）是一种侵袭性的癌症亚型，预后极差。目前尚无可作靶点的遗传驱动事件，该疾病的治疗方案已经超过30年几乎没有改变过了。近期，研究人员通过以CRISPR为基础的筛选方法在SCLC中鉴别可作为潜在治疗靶点的遗传缺陷。研究人员采用单导向RNA（sgRNA）文库，针对被认为编码“可用药”蛋白的约5000个基因，在SCLC、肺腺癌(LUAD)和胰腺导管腺癌(PDAC)的自体基因工程小鼠模型

小细胞肺癌（SCLC）是一种侵袭性的癌症亚型，预后极差。目前尚无可作靶点的遗传驱动事件，该疾病的治疗方案已经超过30年几乎没有改变过了。

近期，研究人员通过以CRISPR为基础的筛选方法在SCLC中鉴别可作为潜在治疗靶点的遗传缺陷。研究人员采用单导向RNA（sgRNA）文库，针对被认为编码“可用药”蛋白的约5000个基因，在SCLC、肺腺癌(LUAD)和胰腺导管腺癌(PDAC)的自体基因工程小鼠模型(GEMMs)的一系列细胞系中进行功能缺失基因筛选。研究人员通过交叉癌症分析检测出SCLC-选择性缺陷。此外，研究人员还观察到SCLC细胞对嘧啶生物合成途径中断的敏感性增强。

药物抑制该通路的关键酶——二氢旋酸脱氢酶(DHODH)，可降低SCLC细胞在体外的生存能力，并可强烈抑制人类患者来源的异种移植(PDX)模型和自体小鼠模型中SCLC肿瘤的生长。

本研究结果提示DHODH抑制或可用作治疗SCLC的方案。

原始出处：

Leanne Li， et al.Identification of DHODH as a therapeutic target in small cell lung cancer.Science Translational Medicine  06 Nov 2019：Vol. 11， Issue 517， eaaw7852.DOI： 10.1126/scitranslmed.aaw7852

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    2020-08-10 bsmagic9140

    #TRA#

    0

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    2020-10-03 ms3025846204744509

    #Transl#

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    2020-01-02 jinweidong

    #特异性#

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    2020-03-31 tongyongming

    #DHODH#

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    2019-11-10 ms3994565386320060

    #Med#

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