Abstract：
It has almost been 40 years since the Ras proteins were discovered as the first human oncogenes. They remain among the most important genes for regulating mammalian cell growth and are involved in more than a quarter of human cancers. Out of 167 members of the Ras superfamily, KRas mutations are the most abundant in human cancers. Particularly, the K-Ras G12C mutations are known to be involved in pancreatic, colon and lung cancers as well as leukemias. Though progress has been made, approaches targeting Ras proteins for therapeutic purposes remain challenging. No drugs treating Ras-related cancers are currently on the market. However, there is now renewed interest in the Ras area, and newer approaches have highlighted the targeting of several types of tumors and treating cancer patients. This review will summarize recent K-Ras drug candidates and approaches in the preclinical, clinical and post-clinical pipelines that show promise for targeting and reducing Ras-related tumors. Macromolecules such as mRNA vaccines, siRNA, and T-cell receptors that target Ras will also be discussed. The newer molecules and the recent approaches to be discussed suggest that the \"undruggable\" era of Ras proteins could be coming to an end.
摘要：
自从Ras蛋白被发现作为第一个人类癌基因以来，已经过去了40年。它们仍然是调节哺乳动物细胞生长的最重要基因之一，并参与超过四分之一的人类癌症。在Ras超家族的167名成员中,KRas突变在人类癌症中是最丰富的。特别是,已知K-RasG12C突变与胰腺有关，结肠癌和肺癌以及白血病。虽然取得了进展,靶向Ras蛋白用于治疗目的的方法仍然具有挑战性。目前市场上没有治疗Ras相关癌症的药物。然而,现在人们对Ras地区重新产生了兴趣,和较新的方法强调了几种类型的肿瘤的靶向和治疗癌症患者。这篇综述将总结最近的K-Ras候选药物和临床前的方法，临床和临床后管道显示出靶向和减少Ras相关肿瘤的希望。大分子如mRNA疫苗，siRNA和靶向Ras的T细胞受体也将被讨论。较新的分子和最近要讨论的方法表明，Ras蛋白的“不可用”时代可能即将结束。
