KRAS mutations are known to be the most recurrent gain-of-function changes instigated in patients with cancer. The RAS gene family is often mutated in most of the human cancers, and the pursuit of inhibitors that bind to mutant RAS continues as a foremost target. RAS is a small GTPase that controls numerous cellular functions, including cell proliferation, growth, survival, and gene expression. RAS is hence closely engaged in cancer pathogenesis. The recent achievements in the discovery of RAS inhibitors imply that the inhibition of RAS oncogene may soon go into clinical trials. This review article describes the role of RAS in cancer drug discovery, the diverse methodologies used to develop direct or indirect RAS inhibitors, and emphasize the current accomplishments in the progress of novel RAS inhibitors. In short, this review focuses on the different attributes of RAS that have been targeted by a range of inhibitors consisting of membrane localization, the active form of RAS, downstream regulator binding, and nucleotide exchange binding. A detailed explanation of RAS and its involvement in cancer drug discovery together with historical aspects are mentioned first followed by a brief outline of the different approaches to target RAS.

已知KRAS突变是癌症患者中最常见的功能获得性改变。在大多数人类癌症中，RAS基因家族经常发生突变，而与突变RAS结合的抑制剂的追求仍是首要目标。RAS是一种小的GTP酶，可控制多种细胞功能，包括细胞增殖，生长，存活和基因表达。因此，RAS与癌症的发病机理密切相关。在发现RAS抑制剂方面的最新成就表明，抑制RAS癌基因可能很快将进入临床试验。这篇综述文章描述了RAS在癌症药物发现中的作用，用于开发直接或间接RAS抑制剂的多种方法，并强调了新型RAS抑制剂进展中的当前成就。简而言之，这篇综述着重于RAS的不同属性，这些属性已被一系列抑制剂所针对，这些抑制剂包括膜定位，RAS的活性形式，下游调节剂结合和核苷酸交换结合。首先提到了RAS及其在癌症药物发现中的参与以及历史方面的详细解释，然后简要介绍了靶向RAS的不同方法。