经济学人下载:钳住癌症的新武器

Oncology and genetics
肿瘤遗传学

Grabbing cancer by the short and curlies
短发卡——钳住癌症的新武器

A new technique for analysing tumours promises better understanding and more effective treatment
一项研究肿瘤的新技术为人类更加深入地了解肿瘤并找到更加有效的治疗方法带来了希望

Sep 24th 2011 | SAN FRANCISCO | from the print edition

ONE of the great hopes nurtured by the Human Genome Project was that it would crack cancer open. Knowing which genes were going wrong would, the theory went, allow specifically tailored drugs to be developed. And this is, indeed, happening. Only last month America’s Food and Drug Administration approved a medicine called Xalkori (generically, crizotinib) for patients who have a particular type of non-small-cell lung cancer, the most common form of that disease. Xalkori blocks the growth of tumours caused by a mutant form of the gene which encodes a signalling molecule known as anaplastic lymphoma kinase. This mutation occurs in 3-5% of lung-cancer patients, and in trials Xalkori caused a dramatic shrinkage of the tumour in around half of those treated.

找到克服癌症的方法，是人类基因组计划带给人们最大的希望之一。理论上，只要找到出错的基因，就能研发出针对它的特定药物。事实上，这些期望正在被逐步实现。就在上个月美国食品药品管理局批准了一种名为Xalkori（通用名：克里唑蒂尼）的新药上市，用于治疗非小细胞肺癌（最常见的一种肺癌）。Xalkori能够抑制由编码信号分子间变性淋巴瘤激酶基因的突变体所导致的癌细胞的增长。3-5%的肺癌患者体内存在这种突变。临床试验中，大约一半受试者在服过此药后体内癌细胞数量显著减少。

The catch is that the respite does not last. Typically, someone will respond for about a year, but after that his tumour starts growing again and the disease continues on its course. This is a pattern seen again and again with the new generation of drugs that genomics has helped to create. They slow the disease, but only for a few months. The presumption is that further mutations are arising in a tumour all the time, and that eventually one of them makes a molecular change that nullifies the effect of the drug. Researchers would dearly like to find a way to deal with this.

但问题是Xalkori对病情的缓解作用持续时间不长。一般来说，持续服药一年后患者将产生抗药性，体内癌细胞恢复增长导致病情恶化。这是一代代利用基因组学开发出的药物共同的治疗效果变化模式，最终都只能短暂地缓解病情。其机制可能是，癌细胞会不断地产生新的突变体，最终其中的某个突变体编码产生了使药物作用失效的蛋白分子。研究人员正致力于找出对付这种机制的办法。