Chen Danyao, Guo Ziyu, Yao Lei, Sun Yuming, Dian Yating, Zhao Deze, Ke Yizhe, Zeng Furong, Zhang Chunfang, Deng Guangtong, Li Linfeng
Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China; National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology, China; Furong Laboratory, Changsha, Hunan, China; Hunan Key Laboratory of Skin Cancer and Psoriasis, Hunan Engineering Research Center of Skin Health and Disease, Xiangya Hospital, Central South University, Changsha, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, China; Department of Thoracic Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China; National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology, China; Furong Laboratory, Changsha, Hunan, China; Hunan Key Laboratory of Skin Cancer and Psoriasis, Hunan Engineering Research Center of Skin Health and Disease, Xiangya Hospital, Central South University, Changsha, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, China.
Redox Biol. 2025 Jul;84:103686. doi: 10.1016/j.redox.2025.103686. Epub 2025 May 19.
Reactive oxygen species (ROS), regulators of cellular behaviors ranging from signaling to cell death, have complex production and control mechanisms to maintain a dynamic redox balance under physiological conditions. Redox imbalance is frequently observed in tumor cells, where ROS within tolerable limits promote oncogenic transformation, while excessive ROS induce a range of regulated cell death (RCD). As such, targeting ROS-mediated regulated cell death as a vulnerability in cancer. However, the precise regulatory networks governing ROS-mediated cancer cell death and their therapeutic applications remain inadequately characterized. In this Review, we first provide a comprehensive overview of the mechanisms underlying ROS production and control within cells, highlighting their dynamic balance. Next, we discuss the paradoxical nature of the redox system in tumor cells, where ROS can promote tumor growth or suppress it, depending on the context. We also systematically explored the role of ROS in tumor signaling pathways and revealed the complex ROS-mediated cross-linking networks in cancer cells. Following this, we focus on the intricate regulation of ROS in RCD and its current applications in cancer therapy. We further summarize the potential of ROS-induced RCD-based therapies, particularly those mediated by drugs targeting specific redox balance mechanisms. Finally, we address the measurement of ROS and oxidative damage in research, discussing existing challenges and future prospects of targeting ROS-mediated RCD in cancer therapy. We hope this review will offer promise for the clinical application of targeting oxidative stress-mediated regulated cell death in cancer therapy.
活性氧（ROS）是细胞行为从信号传导到细胞死亡的调节因子，具有复杂的产生和控制机制，以在生理条件下维持动态的氧化还原平衡。氧化还原失衡在肿瘤细胞中经常被观察到，在肿瘤细胞中，可耐受限度内的ROS促进致癌转化，而过量的ROS则诱导一系列程序性细胞死亡（RCD）。因此，将ROS介导的程序性细胞死亡作为癌症的一个弱点进行靶向治疗。然而，控制ROS介导的癌细胞死亡的精确调控网络及其治疗应用仍未得到充分表征。在本综述中，我们首先全面概述细胞内ROS产生和控制的机制，强调它们的动态平衡。接下来，我们讨论肿瘤细胞中氧化还原系统的矛盾性质，其中ROS根据具体情况既可以促进肿瘤生长也可以抑制肿瘤生长。我们还系统地探讨了ROS在肿瘤信号通路中的作用，并揭示了癌细胞中复杂的ROS介导的交联网络。在此之后，我们重点关注ROS在程序性细胞死亡中的复杂调控及其在癌症治疗中的当前应用。我们进一步总结了基于ROS诱导的程序性细胞死亡疗法的潜力，特别是那些由靶向特定氧化还原平衡机制的药物介导的疗法。最后，我们讨论了研究中ROS和氧化损伤的测量，探讨了在癌症治疗中靶向ROS介导的程序性细胞死亡的现有挑战和未来前景。我们希望这篇综述将为靶向氧化应激介导的程序性细胞死亡在癌症治疗中的临床应用带来希望。
