Classification of KRAS-Activating Mutations and the Implications for Therapeutic Intervention.
Classification of KRAS-Activating Mutations and the Implications for Therapeutic Intervention.
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DOI：
10.1158/2159-8290.cd-22-0035
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发表时间：
2022-04-01
期刊：
影响因子：
28.2
通讯作者：
Haigis KM
中科院分区：
文献类型：
--
作者：
Johnson C;Burkhart DL;Haigis KM
40 多年前发现的 RAS 原癌基因家族是最早发现的癌症起始基因之一。在 RAS 家族的三个成员中，KRAS 是人类癌症中最常见的突变。尽管过去四十年对 RAS 蛋白进行了深入的生物学和生化研究，但我们现在才开始设计针对其致癌特性的治疗策略。在这里，我们强调常见和罕见 KRAS 等位基因的独特生化特性，从而将它们分类为功能亚型。我们还讨论了这种功能分类对于针对突变亚型的潜在治疗途径的影响。
The family of RAS proto-oncogenes, discovered just over 40 years ago, were among the first cancer initiating genes to be discovered. Of the three RAS family members, KRAS is the most frequently mutated in human cancers. Despite intensive biological and biochemical study of RAS proteins over the past four decades, we are only now starting to devise therapeutic strategies to target their oncogenic properties. Here, we highlight the distinct biochemical properties of common and rare KRAS alleles, enabling their classification into functional subtypes. We also discuss the implications of this functional classification for potential therapeutic avenues targeting mutant subtypes.