School of Life Science, Shaoxing University, Shaoxing, Zhejiang, China.
School of Life Science, The Chinese University of Hong Kong, Hong Kong SAR, China.
Int J Cancer. 2023 Sep 1;153(5):918-931. doi: 10.1002/ijc.34486. Epub 2023 Mar 7.
Oncogene-induced hyper-proliferation in cancer cells is accompanied by the onset of different stresses, including DNA-replication stress, metabolic stress and oxidative stress. Excessive accumulation of reactive oxygen species (ROS) plays a pivotal and contradictory role in tumor progression. ROS dictates a multitude of cell signaling pathways to facilitate the malignant transformation of tumor cells. In the meantime, oxidative burden in tumor cells mandates reinforcing antioxidant capacity to mitigate detrimental damages. The addiction to oxidative stress and increased iron demands in cancer cells also impinges on the sensitivity of ferroptosis. Targeting redox homeostasis and ferroptosis to overcome drug resistance in cancer treatment has become an attractive research topic. However, the roles of oncogenic signaling in redox regulation and ferroptosis have not been comprehensively discussed. In this review, we summarize current knowledge regarding the interplay between redox regulation and ferroptosis in the context of cancer biology. We emphasize the implication of oncogenic signaling in redox homeostasis and ferroptosis regulation. We also provide an overview of strategies targeting oxidative stress and ferroptosis in cancer treatment.
致癌基因诱导癌细胞过度增殖会导致多种应激的发生，包括 DNA 复制应激、代谢应激和氧化应激。活性氧（ROS）的过度积累在肿瘤进展中起着关键而矛盾的作用。ROS 通过多种细胞信号通路来促进肿瘤细胞的恶性转化。与此同时，肿瘤细胞的氧化应激负担要求增强抗氧化能力以减轻有害损伤。癌细胞对氧化应激和铁需求的依赖也影响了铁死亡的敏感性。针对氧化还原平衡和铁死亡来克服癌症治疗中的耐药性已成为一个有吸引力的研究课题。然而，致癌信号在氧化还原调节和铁死亡中的作用尚未得到全面讨论。在这篇综述中，我们总结了目前关于癌症生物学中氧化还原调节和铁死亡相互作用的知识。我们强调了致癌信号在氧化还原平衡和铁死亡调节中的作用。我们还概述了针对癌症治疗中氧化应激和铁死亡的策略。
