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Cell:继构建全球很大肺癌细胞库后,他们又找到170种治疗肺癌的潜在药物

2018-04-23 Flora 生物探索

“从超20万种化合物中筛选出170种潜在的抗肺癌药物”——这是美国德克萨斯大学西南医学中心的科学家们最新取得的成果。继构建了全球最大的肺癌细胞库之后,他们利用这一资源,绘制出肺癌遗传突变与潜在药物之间的关联。

“从超20万种化合物中筛选出170种潜在的抗肺癌药物”——这是美国德克萨斯大学西南医学中心的科学家们最新取得的成果。继构建了全球最大的肺癌细胞库之后,他们利用这一资源,绘制出肺癌遗传突变与潜在药物之间的关联。

这一研究以“Chemistry-First Approach for Nomination of Personalized Treatment in Lung Cancer”为题在线发表在《Cell》期刊上。

肺癌是发病率和死亡率最快的恶性肿瘤之一,其中非小细胞肺癌(NSCLC)约占肺癌病例的85%。大多数癌症研究都“聚焦”在基因突变上,但是肿瘤异质性增加了治疗的复杂度。

为了打破局限,UT西南医学中心肿瘤研究Hamon中心主任John Minna教授采用了“化学为先”的模式——从超20万种化合物中筛选到潜在候选药物,并将化合物信息与癌细胞信息匹配,找到非小细胞肺癌的新治疗靶点以及作用于这些靶标的潜在药物。

“对于大部分化合物,我们找到了一套预测性生物标志物,可以助力实现个性化医疗。”John Minna教授解释道。



From left,Dr.Bruce Posner,Dr.Michael Roth,Dr.Michael Peyton,and Dr.John Minna were part of the team scientists who identified 170 chemicals for potential new targets to develop drugs to treat lung cancer.Credit:UT Southwestern Medical Center

1、全球最大的肺癌细胞库

自上世纪70年代,由John Minna教授和研究伙伴、病理学教授Adi Gazdar带领d Hamon肿瘤治疗中心就开始了构建肺癌细胞系的研究项目,并取得了显著成果——建立了全球最大的肺癌细胞库。2015年,为表彰其在肺癌领域的杰出贡献,John Minna教授被誉为“Giant of Cancer Care”。

2、个性化抗癌的“新范式”

现在,研究团队利用这一细胞库筛选能够特异性消灭癌细胞(不损伤正常肺细胞)的化合物。他们制定了“三联”目标:消灭癌细胞的化合物、预测反应的生物标志物、药物积极作用的靶点。研究人员认为这是朝着个性化癌症治疗迈出的重要一步。



图片来源:Cell

具体而言,他们借助于UT西南中心的高通量筛选核心设备——精准肿瘤探测仪(Precision Oncology Probe Set,POPS),共检测了超20万种化合物对抗12种肺癌细胞株的效果。最终,他们从中找到170种化合物。

与此同时,研究团队对肺癌细胞系进行了深入的分子学分析,包括基因突变、蛋白表达鉴定。他们将分子学数据与“单个癌细胞系是否对特定的化合物敏感”的结果相结合,开发出一套生物标志物,作为明确患者肿瘤是否响应这170种化合物中某一种的指标。

下一步,他们将进一步挖掘170种潜在化合物的主要作用机制。此外,研究团队还将检测这些化合物对于其他癌症的作用效果。初步研究显示,一些化合物对于某些类型的乳腺癌卵巢癌有效果。

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    2018-04-25 yxch36
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    2018-04-24 kafei

    学习学习谢谢分享

    0

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    2018-04-23 871538379

    看到治疗肺癌的新希望

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