RAS isoforms and mutations in cancer at a glance
RAS isoforms and mutations in cancer at a glance
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DOI：
10.1242/jcs.182873
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发表时间：
2016-04-01
影响因子：
4
通讯作者：
Rossman, Kent L.
中科院分区：
文献类型：
--
作者：
Hobbs, G. Aaron;Der, Channing J.;Rossman, Kent L.
RAS蛋白（KRAS4A, KRAS4B， NRAS和HRAS）作为gdp - gtp调控的二元开关，调节控制多种正常细胞过程的细胞质信号网络。在大约25%的人类癌症中发现了RAS基因的功能获得错义突变，这促使人们对确定抗RAS治疗策略以治疗癌症产生了兴趣。然而，尽管经过三十多年的努力，抗ras疗法尚未达到临床应用。导致这种失败的原因是低估了RAS的复杂性。首先，现在人们认识到四种人类RAS蛋白在功能上并不相同。其次，随着癌症中发现的bbbb130种不同的错义突变，有一种新兴的观点认为，RAS结构、生物化学和生物学上存在突变特异性后果，需要突变选择性治疗策略。在这篇Cell Science at a Glance文章和随附的海报中，我们提供了RAS亚型和突变之间差异的快照，以及抗RAS药物发现工作的现状。
RAS proteins (KRAS4A, KRAS4B, NRAS and HRAS) function as GDP-GTP-regulated binary on-off switches, which regulate cytoplasmic signaling networks that control diverse normal cellular processes. Gain-of-function missense mutations in RAS genes are found in similar to 25% of human cancers, prompting interest in identifying anti-RAS therapeutic strategies for cancer treatment. However, despite more than three decades of intense effort, no anti-RAS therapies have reached clinical application. Contributing to this failure has been an underestimation of the complexities of RAS. First, there is now appreciation that the four human RAS proteins are not functionally identical. Second, with > 130 different missense mutations found in cancer, there is an emerging view that there are mutation-specific consequences on RAS structure, biochemistry and biology, and mutation-selective therapeutic strategies are needed. In this Cell Science at a Glance article and accompanying poster, we provide a snapshot of the differences between RAS isoforms and mutations, as well as the current status of anti-RAS drug-discovery efforts.