RAS proteins are critical regulators of signaling networks controlling diverse cellular functions such as cell proliferation and survival and its mutation are among the most powerful oncogenic drivers in human cancers. Despite intense efforts, direct RAS-targeting strategies remain elusive due to its “undruggable” nature. To that end, bulk of the research efforts has been directed towards targeting upstream and/or downstream of RAS signaling. However, the therapeutic efficacies of these treatments are limited in the long run due to the acquired drug resistance in RAS-driven cancers. Interestingly, recent studies have uncovered a potential role of RAS in redox-regulation as well as the interplay between ROS and RAS-associated signaling networks during process of cancer initiation and progression. More specifically, these studies provide ample evidence to implicate RAS as a redox-rheostat, manipulating ROS levels to provide a redox-milieu conducive for carcinogenesis. Importantly, the understanding of RAS-ROS interplay could provide us with novel targetable vulnerabilities for designing therapeutic strategies. In this review, we provide a brief summary of the advances in the field to illustrate the dual role of RAS in redox-regulation and its implications in RAS signaling outcomes and also emerging redox-based strategies to target RAS-driven cancers.

RAS蛋白是控制多种细胞功能（例如细胞增殖和存活）的信号网络的关键调节剂，其突变是人类癌症中最强大的致癌驱动因素之一。尽管付出了巨大的努力，但由于RAS的“不起眼的”性质，直接针对RAS的策略仍然难以实现。为此，大部分研究工作已针对以RAS信号传导的上游和/或下游为目标。然而，由于在RAS驱动的癌症中获得的耐药性，从长远来看，这些疗法的治疗效果受到限制。有趣的是，最近的研究发现了RAS在氧化还原调节中的潜在作用，以及在癌症发生和发展过程中ROS与RAS相关信号网络之间的相互作用。进一步来说，这些研究提供了充分的证据来暗示RAS是氧化还原变阻器，操纵ROS的水平以提供有利于癌变的氧化还原-milieu。重要的是，对RAS-ROS相互作用的理解可以为我们设计治疗策略提供新的针对性漏洞。在这篇综述中，我们简要概述了该领域的进展，以说明RAS在氧化还原调节中的双重作用及其在RAS信号转导中的作用，以及针对RAS驱动的癌症的新兴基于氧化还原的策略。