经济学人下载:钳住癌症的新武器

In fact, he found three. Mediator-12 (MED 12), which helps to transcribe genes from DNA into RNA messengers, was one. The other two were genes that help maintain the structure of chromosomes. Presumably, resistance to Xalkori is being caused by disabling mutations in one or more of these genes.

实际上，伯纳兹博士最后确认了三个。一个是Mediator-12(MED 12)，即控制基因转录成信使RNA的中介体复合物亚基12基因，其他两个是帮助维护持染色体结构的基因。可以推断，针对Xalkori的抗药性是由于这三个基因中的一个或多个发生了突变导致的结果。

That is interesting, but not of immediate assistance to the dying. What Dr Bernards and his colleagues did next, though, could be of such help. They looked for hairpin RNAs that restored sensitivity to Xalkori in cells whose MED12 messengers were being blocked—and they found one. Disabling the messengers of the gene that encodes a receptor protein called TGF beta-R2, which is found on cell surfaces, caused cells that had once been resistant to Xalkori to shrivel in its presence. Moreover, treating these same Xalkori-resistant cells with an experimental drug designed to block TGF beta-receptors restored sensitivity to Xalkori, though it had no effect on cancer-cell growth on its own.

这个发现十分有趣，但是对治疗患者没有直接帮助。伯纳兹博士与同事们接下来所做的工作正符合这个目的。他们尝试寻找能够拦截MED12基因的信使RNA从而恢复细胞对Xalkori敏感性的发夹结构，并取得了成功。TGF beta-R2是一种存在于细胞表面的蛋白质受体，只要破坏编码这种受体DNA的信使RNA，就能消除细胞对Xalkori的抗药性。此外，设计药物针对同样的抗药细胞，使其表面的TGF beta受体被药物屏蔽，也会得到相同的实验结果，即使这种药物本身并没有阻止癌细胞增长的疗效。

Dr Bernards thinks that in MED12 he has discovered a pathway crucial for the development of drug resistance. Subsequent studies by members of his group have found that interfering with MED12 messengers causes resistance to numerous other drugs. These include Iressa and Tarceva, which are prescribed for lung cancer; Zelboraf, which is effective against melanoma; and Nexavar, which is used for kidney and liver cancers. If these lab-based results are confirmed in people then TGF beta-receptor inhibitors may prove a way of extending the useful lives of a plethora of medicines.

伯纳兹博士认为，通过MED12基因他找出了一个对于细胞产生抗药性十分关键的路径。伯纳兹博士的研究组同事在随后的研究中发现，干扰MED12基因的信使RNA会导致产生对多种药物的抗药性，包括用于治疗肺癌的药物易瑞沙（Iressa）和特罗凯（Tarceva）、黑色素瘤药物左博拉（Zelboraf）以及肾癌和肝癌药物多吉美（Nexavar）。如果这项实验结果在人体内也得到证实，TGF beta受体抑制剂将被用来延长多种药物的使用寿命。

Dr Bernards’s work, indeed, is just the vanguard. At least three other groups of researchers are using short hairpin RNA to study cancer in this way, and one of them, led by William Hahn of the Dana-Farber Cancer Institute in Boston, has already found what may be an important molecular link in the development of ovarian tumours. Turning these sorts of laboratory discoveries into treatments is a long and tedious process that often fails. What is crucial about Dr Bernards’s work, though, is that short hairpin RNAs do exactly what the genome project promised: they crack the problem open.

伯纳兹博士的研究工作只是这个领域的先头部队，同期至少还有其他三组人也在利用短发卡RNA朝相同方向进行肿瘤研究。其中，由威廉姆.哈恩带领的波斯顿法波癌症研究院研究小组，已经发现可能对卵巢癌发生过程十分重要的分子链。将实验室发现的成果运用到实际治疗中是一个冗长而乏味的过程，其中伴随着无数次失败。而伯纳兹博士的研究工作的决定性意义是，短发卡RNA正像人类基因组计划承诺的那样，找到了问题的突破点。