McCormick Frank
Frederick National Laboratory for Cancer Research, Frederick, Maryland. UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, California.
Clin Cancer Res. 2015 Apr 15;21(8):1797-801. doi: 10.1158/1078-0432.CCR-14-2662.
KRAS proteins play a major role in human cancer, but have not yielded to therapeutic attack. New technologies in drug discovery and insights into signaling pathways that KRAS controls have promoted renewed efforts to develop therapies through direct targeting of KRAS itself, new ways of blocking KRAS processing, or by identifying targets that KRAS cancers depend on for survival. Although drugs that block the well-established downstream pathways, RAF-MAPK and PI3K, are being tested in the clinic, new efforts are under way to exploit previously unrecognized vulnerabilities, such as altered metabolic networks, or novel pathways identified through synthetic lethal screens. Furthermore, new ways of suppressing KRAS gene expression and of harnessing the immune system offer further hope that new ways of treating KRAS are finally coming into view. These issues are discussed in this edition of CCR Focus.
KRAS蛋白在人类癌症中起主要作用，但尚未成为治疗靶点。药物研发的新技术以及对KRAS所控制信号通路的深入了解，促使人们重新努力，通过直接靶向KRAS本身、阻断KRAS加工的新方法或识别KRAS相关癌症生存所依赖的靶点来开发治疗方法。尽管阻断成熟下游通路RAF-MAPK和PI3K的药物正在临床中进行测试，但人们正在努力利用以前未被认识到的弱点，如代谢网络改变，或通过合成致死筛选确定的新通路。此外，抑制KRAS基因表达和利用免疫系统的新方法为最终出现治疗KRAS的新方法带来了更多希望。本期《临床肿瘤研究聚焦》将对这些问题进行讨论。
