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科学家发现21种全新潜在药物靶点

2017-09-04 佚名 新浪

来自瑞典的科学家在8月的《科学》杂志上发表文章,通过对9,666人的基因测序的研究,分析17种癌症的转录组学、蛋白质组学和临床数据,得到了人类癌症病理学图集。

来自瑞典的科学家在8月的《科学》杂志上发表文章,通过对9,666人的基因测序的研究,分析17种癌症的转录组学、蛋白质组学和临床数据,得到了人类癌症病理学图集。



(人类癌症病理学图集构建方法)

总体上来说,如果与细胞生长相关的基因上调或者与细胞分化相关的基因下调,那么病人的生存期便会缩短。通过全基因组代谢模型(genome-scale metabolic models, GSMM),研究人员发现不同病人的代谢差异性比较大,这种现象在不同的癌症中是普遍存在的。所以,精准治疗和个性化治疗对于癌症来说非常重要。

研究还发现,不同基因在病人体内的表达差别很大。以三羧酸循环为例,延胡索酸酶(FH)在几乎所有的肝癌病人中都是一个保守的肿瘤生长基因,而ATP-柠檬酸裂解酶(ACLY)只在不到5%的病人中是一个关键的肿瘤生长基因。



(肝癌病人的三羧酸循环基因表达图)

从上图还可以看到,在大多数(>80%)癌症病人体内都作为保守的必需基因(essential genes)并不多。通过分析其他癌症,科学家也发现了类似的结论,保守的必需基因并不多,只占10-25%。



(各种主要癌症中重要基因的比例)

问题是:这些保守的必需基因能不能作为药物靶点呢?因为对于正常组织来说,这2553个必需基因大多数有着非常重要的代谢作用。有预测,这些蛋白如果被抑制,则80%会产生严重的不良反应。

尽管许多质疑,科学家还是从中预测32个可能的药物靶点。这些靶点对于正常组织没有毒性,而对超过80%的病人的肿瘤生长起着关键作用。



(预测的32个代谢基因。这些基因对17种癌症的肿瘤生长是必需的)

细细分析这32个基因可以发现,大多数基因参与了核酸的代谢。据生物世纪(BioCentury)的BCIQ数据库统计,其中21种基因还没有被任何公司进行药物开发。

这21个全新的靶点包括10个DNA或者RNA聚合酶,4个激酶,还有其他一些蛋白。

这些全新的靶点无疑是一个巨大的宝藏。至于是否能成为成功的药物靶点,让我们一起期待吧。

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    2017-09-06 xugc
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    2017-09-05 130****4638

    学习了谢谢分享

    0

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    2017-09-04 lovetcm

    不一定是每一个target都有临床应用价值

    0

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