文章：

靶向丝裂原活化蛋白激酶级联治疗癌症

Targeting the mitogen-activated protein kinase cascade to treat cancer

原文发布日期：2004-12-01

DOI: 10.1038/nrc1503

类型: Review Article

开放获取: 否

要点：

1. The mitogen-activated protein kinase (MAPK) pathway controls the growth and survival of a broad spectrum of human tumours.
2. Activating mutations in RAS and RAF result in activation of the MAPK pathway and are present in a large percentage of solid tumours.
3. The central role of RAF and MAPK kinase (MEK) in transmitting signals through the RAS–MAPK pathway make these kinases promising targets of anticancer drugs.
4. MEK inhibitors are the first highly selective inhibitors of the MAPK pathway to enter the clinic.
5. Emerging clinical data show promising hints that suppression of the MAPK pathway can be achieved without unacceptable toxicity levels.

要点翻译：

1. 丝裂原活化蛋白激酶（MAPK）通路调控多种人类肿瘤的生长与存活。
2. RAS和RAF的激活突变可导致MAPK通路活化，该突变存在于大部分实体瘤中。
3. RAF与MAPK激酶（MEK）在RAS-MAPK信号传导中的核心作用，使这些激酶成为抗癌药物的理想靶点。
4. MEK抑制剂是首批进入临床的高选择性MAPK通路抑制剂。
5. 最新临床数据显示，在不产生不可接受毒性水平的前提下抑制MAPK通路已显现出良好前景。

英文摘要：

The RAS–mitogen activated protein kinase (MAPK) signalling pathway has long been viewed as an attractive pathway for anticancer therapies, based on its central role in regulating the growth and survival of cells from a broad spectrum of human tumours. Small-molecule inhibitors designed to target various steps of this pathway have entered clinical trials. What have we recently learned about their safety and effectiveness? Will the MAPK pathway prove amenable to therapeutic intervention?

摘要翻译： 

RAS–丝裂原活化蛋白激酶（MAPK）信号通路因其在调控多种人类肿瘤细胞生长与存活中的核心作用，长期以来一直被视为抗癌治疗的重要靶点。针对该通路多个环节设计的小分子抑制剂已进入临床试验阶段。我们近期对其安全性与有效性有哪些新的认识？MAPK通路是否真的适合治疗干预？

原文链接：

Targeting the mitogen-activated protein kinase cascade to treat cancer