KRAS 等位基因：细节决定成败。
KRAS Alleles: The Devil Is in the Detail.
作者信息
Haigis Kevin M
机构信息
Cancer Research Institute, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA; Department of Medicine, Harvard Medical School, Boston, MA 02215, USA.
出版信息
Trends Cancer. 2017 Oct;3(10):686-697. doi: 10.1016/j.trecan.2017.08.006. Epub 2017 Sep 12.
Abstract
KRAS is the most frequently mutated oncogene in cancer and KRAS mutation is commonly associated with poor prognosis and resistance to therapy. Since the KRAS oncoprotein is, as yet, not directly druggable, efforts to target KRAS mutant cancers focus on identifying vulnerabilities in downstream signaling pathways or in stress response pathways that are permissive for strong oncogenic signaling. One aspect of KRAS biology that is not well appreciated is the potential biological differences between the many distinct KRAS activating mutations. This review draws upon insights from both clinical and experimental studies to explore similarities and differences among KRAS alleles. Historical and emerging evidence supports the notion that the specific biology related to each allele might be exploitable for allele-specific therapy.
摘要
KRAS是癌症中最常发生突变的致癌基因，KRAS突变通常与预后不良和治疗耐药相关。由于KRAS癌蛋白目前尚不能直接成药，针对KRAS突变癌症的研究致力于在下游信号通路或应激反应通路中寻找对强大致癌信号传导具有允许作用的脆弱环节。KRAS生物学中一个尚未得到充分认识的方面是，许多不同的KRAS激活突变之间可能存在生物学差异。本综述借鉴临床和实验研究的见解，探讨KRAS等位基因之间的异同。历史和新出现的证据支持这样一种观点，即与每个等位基因相关的特定生物学特性可能可用于等位基因特异性治疗。
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