最新Nature封面 抗癌总动员

　　

生物通报道，最新一期的Nature杂志（4月9日）公布了一系列的癌症研究进展的综述文章与研究性论文，本期的封面标题为Cancer Future，这是继上一期Nature癌症专题以后，又一次大篇幅的介绍癌症的研究成果。发起了抗癌的总动员。

 

全新的癌症治疗路径

其中一篇抗癌新药的研究值得关注，主要讲述以 “泛素-蛋白酶”为靶位的抗癌新药物。文章由来自Millennium Pharmaceuticals公司的科学家发表，介绍了一种全新的治疗癌症的方式。

 

文章标题为：An inhibitor of NEDD8-activating enzyme as a new approach to treat cancer。研究者们新发现一种与癌症相关的蛋白酶体抑制因子，它正成为一种新的抗肿瘤药物，首次报告被用于临床的蛋白酶体抑制因子是 “硼替佐米”（Bortezomib），用来治疗多种骨髓瘤和一些淋巴瘤。

 

这篇文章中Soucy等人报告了MLN4924，它是“NEDD8-激发酶”（NAE）的一个小分子抑制因子，目前正在进行一期临床试验。NAE调控“泛素连接酶”一种亚型（即cullin-RING）的活性，后者又控制各种不同细胞蛋白的降解。MLN4924在小鼠癌症模型中诱导癌细胞死亡和产生抗肿瘤活性。

 

这为抗肿瘤药物的设计开辟了新的道路。

文章摘要

The clinical development of an inhibitor of cellular proteasome function suggests that compounds targeting other components of the ubiquitin–proteasome system might prove useful for the treatment of human malignancies. NEDD8-activating enzyme (NAE) is an essential component of the NEDD8 conjugation pathway that controls the activity of the cullin-RING subtype of ubiquitin ligases, thereby regulating the turnover of a subset of proteins upstream of the proteasome. Substrates of cullin-RING ligases have important roles in cellular processes associated with cancer cell growth and survival pathways. Here we describe MLN4924, a potent and selective inhibitor of NAE. MLN4924 disrupts cullin-RING ligase-mediated protein turnover leading to apoptotic death in human tumour cells by a new mechanism of action, the deregulation of S-phase DNA synthesis. MLN4924 suppressed the growth of human tumour xenografts in mice at compound exposures that were well tolerated. Our data suggest that NAE inhibitors may hold promise for the treatment of cancer.

 

 

近20年抗癌成果集锦

另外本期的一篇综述文章（第719页）回顾了上个世纪80年代初以来癌症遗传学领域所取得的进展，展望了我们今后几年在癌症基因组学领域所可能看到的进展。

 

文章标题为：The cancer genome

All cancers arise as a result of changes that have occurred in the DNA sequence of the genomes of cancer cells. Over the past quarter of a century much has been learnt about these mutations and the abnormal genes that operate in human cancers. We are now, however, moving into an era in which it will be possible to obtain the complete DNA sequence of large numbers of cancer genomes. These studies will provide us with a detailed and comprehensive perspective on how individual cancers have developed.