Técher Hervé, Kemiha Samira, Aobuli Xieraili, Kolinjivadi Arun Mouli
Université Côte d'Azur, Institute for Research on Cancer and Aging of Nice-IRCAN, CNRS, INSERM, 06100 Nice, France.
Lee Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33612, USA.
Cancers (Basel). 2024 Nov 28;16(23):3993. doi: 10.3390/cancers16233993.
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.
四十多年来，大鼠肉瘤（RAS）驱动的癌症一直是癌症科学领域的主要研究焦点之一。尽管在理解RAS致癌基因生物学方面取得了显著进展，但靶向RAS突变癌症的方法仍不明确。近年来，RAS在其过度增殖之外的作用已得到广泛记载。在本综述中，我们系统地阐述并详述了RAS致癌基因介导的DNA复制和DNA损伤反应（DDR）途径改变的机制细节，重点关注肺癌。我们进一步将这种分子联系扩展到RAS成瘾性癌症中的胞质DNA积累、先天免疫激活和衰老。最后，我们简要推测了靶向RAS突变肺癌的潜在策略，考虑了针对DNA复制、DNA修复和cGAS-STING促炎途径的各种方法。这些新的治疗方法，尤其是联合使用时，可能会提高治疗效果并克服与这些突变相关的挑战。
