Rat Sarcoma (RAS)-driven cancers have been one of the main foci in the field of cancer science for over four decades. Despite significant improvement in understanding the biology of RAS oncogene, the method to target RAS-mutated cancers is still unclear. In recent years, the role for RAS beyond its hyperproliferation has been extensively documented. In this review, we systematically address and dwell on the details of the mechanisms of RAS oncogene-mediated alteration in the DNA replication and DNA damage response (DDR) pathways, focusing on lung cancers. We further extend this molecular connection towards cytosolic DNA accumulation, innate immune activation and senescence in RAS-addicted cancers. At the end, we briefly speculate on the potential strategies for targeting RAS mutated lung cancers, considering various approaches targeting DNA replication, DNA repair and the cGAS-STING pro-inflammatory pathway. These new lines of therapy, especially when used in combinations, may enhance treatment efficacy and overcome the challenges associated with these mutations.
鼠类肉瘤病毒癌基因（RAS）驱动的癌症在过去四十余年中一直是癌症科学领域的主要关注点之一。尽管对RAS癌基因生物学的理解已取得显著进展，但针对RAS突变癌症的治疗方法仍不明确。近年来，RAS在促进细胞过度增殖之外的作用已得到广泛证实。本综述系统阐述并深入探讨了RAS癌基因介导的DNA复制及DNA损伤应答（DDR）通路改变机制，重点关注肺癌领域。我们进一步将这种分子机制延伸至RAS依赖性癌症中的胞质DNA积累、天然免疫激活及细胞衰老过程。最后，结合靶向DNA复制、DNA修复以及cGAS-STING促炎通路等多种策略，我们简要探讨了针对RAS突变肺癌的潜在治疗方向。这些新型治疗方案，特别是联合应用时，有望提升治疗效果并克服由这些突变带来的治疗挑战。
Oncogenic RAS in Cancers from the DNA Replication Stress and Senescence Perspective
肿瘤(癌症)患者之家