Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, P.O. Box B, Frederick, MD 21702, USA.
Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, P.O. Box B, Frederick, MD 21702, USA; UCSF Helen Diller Family Comprehensive Cancer Center, Room 371, 1450 3(rd) Street, P.O. Box 589001, San Francisco, CA 94158-9001, USA.
Cancer Cell. 2014 Mar 17;25(3):272-81. doi: 10.1016/j.ccr.2014.02.017.
Ras proteins play a major role in human cancers but have not yielded to therapeutic attack. Ras-driven cancers are among the most difficult to treat and often excluded from therapies. The Ras proteins have been termed "undruggable," based on failures from an era in which understanding of signaling transduction, feedback loops, redundancy, tumor heterogeneity, and Ras' oncogenic role was poor. Structures of Ras oncoproteins bound to their effectors or regulators are unsolved, and it is unknown precisely how Ras proteins activate their downstream targets. These knowledge gaps have impaired development of therapeutic strategies. A better understanding of Ras biology and biochemistry, coupled with new ways of targeting undruggable proteins, is likely to lead to new ways of defeating Ras-driven cancers.
Ras 蛋白在人类癌症中起着重要作用，但尚未能进行治疗性攻击。Ras 驱动的癌症是最难治疗的癌症之一，通常被排除在治疗之外。基于对信号转导、反馈回路、冗余、肿瘤异质性和 Ras 致癌作用理解不足的时代的失败，Ras 蛋白被称为“不可成药”。Ras 致癌蛋白与其效应物或调节剂结合的结构尚未解决，也不知道 Ras 蛋白如何精确激活其下游靶标。这些知识空白阻碍了治疗策略的发展。更好地理解 Ras 的生物学和生物化学，以及针对不可成药蛋白的新方法，可能会导致战胜 Ras 驱动的癌症的新方法。
