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NCI发布最大规模癌症相关基因变异数据库
时间:2013-07-17 09:40:20 来源:生物谷 点击:
美国国家癌症研究所(NCI)科学家发布了有史以来规模最大的癌症相关基因变异数据库,为研究者们提供了迄今为止最全面的方式,搞清楚如何将治疗药物靶向疾病。

周一NCI在一份声明中称,基于基因组学研究的新数据库,将对全球开放获取,预计将有助于研究人员加快新药的开发,同时能够更好地将患者与疗法进行匹配。

当前所使用的大多数抗癌药物,都是基于其实证作用(empirical activity)。其中的大多数药物,我们知道存在作用靶标,但这些药物并没有与任何基因组学联系起来。

大多数的癌症治疗涉及很多的猜测工作,因为医生也没有办法确定某一特定患者是否有可能对当前许多常用药物或化疗有响应,抑或其癌症是否会对所用药物产生抗性。

为了创建数据库,NCI研究团队对60株人类癌细胞系进行了测序,得到了一张针对身体不同部位癌症特异性基因突变的详尽列表。

该项研究的成果已发表于美国癌症研究协会期刊《癌症研究》(Cancer Research)。

研究人员现在可以对数据库进行挖掘,比如确定化疗药物顺铂(Cisplatin)是否与特定的基因突变有关联。而目前已知,仅有约一半的女性卵巢癌对顺铂有反应,制药公司则可能不会受到很大的激励,来确定是否一种现有的癌症药物应该仅应用于某一亚组(subset)患者群体。

近年来,许多获批的抗癌药物均为靶向治疗药物,这些药物旨在阻断癌细胞用于生长和增殖的特定通路。在给药前,对患者进行特定基因突变的筛查,可能能够使某些患者获得最大的治疗益处。

例如,由罗氏(Roche)销售的一款黑色素瘤药物Zelboraf,旨在靶向一种特定的基因突变,该突变存在于大约一半的黑色素瘤中。辉瑞(Pfizer)的抗癌药物Xalkori,则靶向于ALK基因中的一种突变,该药仅对约4%的肺癌患者有效。

英文原文:Largest cancer gene database made public

Mon Jul 15, 2013 7:22pm EDT National Cancer Institute scientists have released the largest-ever database of cancer-related genetic variations, providing researchers the most comprehensive way so far to figure out how to target treatments for the disease.

Open access worldwide to the new database, based on genome studies, is expected to help researchers accelerate development of new drugs and better match patients with therapies, NCI said in a statement on Monday.

"Most anti-cancer drugs that are used today are used based on their empirical activity," Dr. Yves Pommier, chief of the NCI's Laboratory of Molecular Pharmacology, said in an interview. "For most of them, we know there is a target, but they have not been connected with any genomics."

Most cancer treatments involve a lot of guess work because doctors have no way to determine how a particular patient is likely to respond to many commonly used drugs or chemotherapy, or which cancers will develop resistance.

To create the database, the NCI team sequenced 60 human cancer cell lines, generating an extensive list of cancer-specific variations for different parts of the body.

The results were published in Cancer Research, a journal of the American Association for Cancer Research.

Researchers could mine the data, for instance, to determine whether the chemotherapy drug Cisplatin is associated with specific genetic mutations, Pommier said.

"Only about half of women with ovarian cancer respond to it," he said, noting that pharmaceutical companies would have little incentive to determine if an existing cancer drug should only be used in a subset of patients.

Many recently approved cancer drugs are targeted treatments, designed to block specific pathways that cancer cells use to grow and reproduce. Before the drugs are administered, patients are tested for the specific genetic mutations that would make the drug more likely to be beneficial to them.

Melanoma drug Zelboraf, sold by Roche Holding AG, is designed to work by targeting a specific genetic mutation found in about half of all melanomas. Pfizer Inc's cancer drug Xalkori, which targets a mutation in the ALK gene, works in about 4 percent of lung cancer patients.

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