Ras proteins play a crucial role as a central component of the cellular networks controlling a variety of signaling pathways that regulate growth, proliferation, survival, differentiation, adhesion, cytoskeletal rearrangements and motility of a cell. Almost, 4 decades passed since Ras research was started and ras genes were originally discovered as retroviral oncogenes. Later on, mutations of the human RAS genes were linked to tumorigenesis. Genetic analyses found that RAS is one of the most deregulated oncogenes in human cancers. In this review, we summarize the pioneering works which allowed the discovery of RAS oncogenes, the finding of frequent mutations of RAS in various human cancers, the role of these mutations in tumorigenesis and mutation-activated signaling networks. We further describe the importance of RAS mutations in personalized or precision medicine particularly in molecular targeted therapy, as well as their use as diagnostic and prognostic markers as therapeutic determinants in human cancers.

Ras蛋白作为控制各种信号通路的细胞网络的核心组成部分，这些信号通路调节着细胞的生长，增殖，存活，分化，粘附，细胞骨架重排和运动。自从Ras研究开始以来已经过去了近40年，最初发现ras基因是逆转录病毒致癌基因。后来，人类RAS基因的突变与肿瘤发生有关。遗传分析发现，RAS是人类癌症中最失控的致癌基因之一。在这篇综述中，我们总结了开创性的工作，这些发现允许发现RAS致癌基因，发现频繁的RAS突变。在各种人类癌症中，这些突变在肿瘤发生和突变激活信号网络中的作用。我们进一步描述了RAS突变在个性化或精密医学中，特别是在分子靶向治疗中的重要性，以及它们作为诊断和预后标志物作为人类癌症中治疗决定因素的用途。