经济学人下载:钳住癌症的新武器

One who is trying to do so is Rene Bernards of the Netherlands Cancer Institute. On September 18th he told a meeting of the American Association for Cancer Research, held in San Francisco, about a way that the sensitivity of tumour cells to Xalkori might be restored. More important than that, though, is the way he discovered the solution—for this could be applied to many other cases in which an anti-cancer drug is having its useful life curtailed by the development of resistance.

来自荷兰癌症研究所的勒内.伯纳兹博士便是其中一位。9月18日，他在旧金山一个由美国癌症研究协会组织的研讨会上宣布，发现了使癌细胞恢复对Xalkori敏感性的方法。然而比这更具意义的是，此种方法的原理，同样适用于打破其他多种由于产生抗药性而导致其疗效减退的抗癌药物所遭遇的瓶颈。

One of the problems with cancer is that the mutations which cause it are often hidden in a plethora of others that have no direct bearing on the disease. Normal DNA sequencing cannot distinguish which mutations are important and which are not. Dr Bernards, however, thinks he can, by using molecules called short hairpin RNAs.

攻克癌症的困难之一，是致癌突变通常都隐藏在其他众多非致癌突变之中，而正规的DNA测序不能检测区别出两者的不同。不过现在，伯纳兹博士称，利用一种叫做短发夹RNA的分子，他找到了区别二者的方法。

On the pin money
深入探究

RNA is a molecule similar to DNA, except that its molecules are usually much smaller. One of its jobs is to act as a messenger carrying genetic information from a cell’s nucleus to the machinery which makes proteins. Each messenger is an edited copy of one strand of the DNA double helix. Double-stranded RNA does exist, but mostly in viruses. Mammalian cells make only the single-stranded variety. If a cell’s defence mechanisms detect double-stranded RNA they destroy it, to protect against infection.

RNA是一种类似于DNA的分子，但是其分子量比DNA小得多。它的职能之一是充当信使将遗传信息从细胞核运送至制造蛋白质的机器——核糖体。每一个信使RNA都是由双螺旋DNA的一个单链编码转录而成。双链RNA通常只存在于病毒体内。哺乳动物细胞只能正常识别单链RNA，如果发现双链RNA就会迅速将其销毁，以保护机体免受病毒感染。

This aversity to double-stranded RNA means short hairpins can be used to knock out the messengers, thus nullifying the signal from the underlying gene. It is just a question of making a hairpin with an appropriate genetic sequence—one that is the same as the missing strand of the original DNA—so that the hairpin will combine eagerly with the messenger to form a double-stranded molecule. Modern gene-synthesis techniques mean this is not hard to do. Dr Bernards therefore did it with the messengers of 20,000 genes, to see which, if any, are implicated in the development of resistance to Xalkori.

机体对双链RNA的排斥性意味着可以利用短发卡RNA破坏信使RNA，从而阻断相应基因的信号传递。问题的关键是设计出合适的发卡结构，其遗传序列必须与其替代的DNA序列一致，才能迅速准确地结合其编码的RNA成为双链RNA分子。利用DNA合成技术很容易完成这项任务。因此，伯纳兹博士对2000个基因的信使RNA进行一一实验，以确认与产生Xalkori抗药性有关的基因是否存在其中、是具体的哪一个。