KRAS: The Critical Driver and Therapeutic Target for Pancreatic Cancer.

KRAS: The Critical Driver and Therapeutic Target for Pancreatic Cancer.
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KRAS:胰腺癌的关键驱动力和治疗靶标。

DOI:
10.1101/cshperspect.a031435
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发表时间:
2018-09-04
影响因子:
5.4
通讯作者:
Der CJ
Der CJ
中科院分区:
医学2区
文献类型:
--
作者:
Waters AM;Der CJ

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RAS基因(HRAS、KRAS和NRAS)是人类癌症中最常发生突变的癌基因家族。在美国,导致癌症死亡的前三大原因(肺癌、结直肠癌和胰腺癌)中,RAS突变频率最高,因此开发抗RAS疗法是癌症研究的主要重点。尽管经过了30多年的努力,还没有一种有效的RAS抑制剂能够应用到癌症患者身上。有了从过去的失败中吸取的惨痛教训,有了新的想法和战略,人们重新燃起了希望,认为无法下药的RAS可能最终会被征服。由于KRAS异构体在84%的ras突变型癌症中发生突变,我们将重点放在KRAS上。由于KRAS突变频率接近100%,胰腺导管腺癌(PDAC)被认为是所有癌症中最依赖ras的。我们综述了KRAS作为PDAC的驱动因子和治疗靶点的作用。
RAS genes (HRAS, KRAS, and NRAS) comprise the most frequently mutated oncogene family in human cancer. With the highest RAS mutation frequencies seen with the top three causes of cancer deaths in the United States (lung, colorectal, and pancreatic cancer), the development of anti-RAS therapies is a major priority for cancer research. Despite more than three decades of intense effort, no effective RAS inhibitors have yet to reach the cancer patient. With bitter lessons learned from past failures and with new ideas and strategies, there is renewed hope that undruggable RAS may finally be conquered. With the KRAS isoform mutated in 84% of all RAS-mutant cancers, we focus on KRAS. With a near 100% KRAS mutation frequency, pancreatic ductal adenocarcinoma (PDAC) is considered the most RAS-addicted of all cancers. We review the role of KRAS as a driver and therapeutic target in PDAC.
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