Dragging Ras Back in the Ring
Dragging Ras Back in the Ring
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DOI：
10.1016/j.ccr.2014.02.017
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发表时间：
2014-03-17
期刊：
影响因子：
50.3
通讯作者：
McCormick, Frank
中科院分区：
文献类型：
--
作者：
Stephen, Andrew G.;Esposito, Dominic;McCormick, Frank
Ras蛋白在人类癌症中起主要作用，但尚未屈服于治疗攻击。Ras驱动的癌症是最难治疗的癌症之一，通常被排除在治疗之外。Ras蛋白被称为“不可治疗的”，这是基于对信号转导、反馈环、冗余、肿瘤异质性和Ras致癌作用的理解不足的时代的失败。Ras癌蛋白与其效应子或调节子结合的结构尚未解决，Ras蛋白如何激活其下游靶点也不清楚。这些知识差距阻碍了治疗策略的发展。更好地了解Ras生物学和生物化学，再加上靶向不可治疗蛋白质的新方法，可能会导致击败Ras驱动的癌症的新方法。
Ras proteins play a major role in human cancers but have not yielded to therapeutic attack. Ras-driven cancers are among the most difficult to treat and often excluded from therapies. The Ras proteins have been termed "undruggable," based on failures from an era in which understanding of signaling transduction, feedback loops, redundancy, tumor heterogeneity, and Ras' oncogenic role was poor. Structures of Ras onco-proteins bound to their effectors or regulators are unsolved, and it is unknown precisely how Ras proteins activate their downstream targets. These knowledge gaps have impaired development of therapeutic strategies. A better understanding of Ras biology and biochemistry, coupled with new ways of targeting undruggable proteins, is likely to lead to new ways of defeating Ras-driven cancers.