Liu Yu'e, Wu Guangzhen, Feng Linjing, Li Jialing, Xia Yuyang, Guo Wenjia, Zhao Kaijun
Department of Neurosurgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200120, China.
Boston Children's Hospital, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
Antioxidants (Basel). 2025 May 31;14(6):674. doi: 10.3390/antiox14060674.
Antioxidants neutralize reactive oxygen species and free radicals, protecting cells from oxidative damage and maintaining cellular homeostasis. In cancer therapy, they play a complex dual role, serving as protective agents against oxidative stress while, under certain conditions, acting as pro-oxidants that may promote tumorigenesis and resistance to treatment. Redox regulation is governed by key antioxidant pathways, such as the BACH1 and NRF2 pathways, along with transcriptional factors that significantly affect cancer progression and immunotherapy response. In addition to their intracellular effects, antioxidants modulate the tumor microenvironment, including interactions with the extracellular matrix, which impact cancer cell behavior and therapeutic responses. This review also explores preclinical studies that investigate the roles of major antioxidants in cancer biology. While these studies present promising data, significant challenges persist, including the potential for antioxidants to interfere with standard cancer treatments or to inadvertently support tumor survival. We further highlight emerging strategies aimed at optimizing antioxidant therapy, including personalized medicine approaches, nanoparticle-based delivery systems, and combination treatments with immunotherapies and targeted therapies. By examining the therapeutic potential and associated risks of antioxidants, this review provides critical insights into their role in cancer treatment and offers a roadmap for advancing antioxidant-based strategies to improve clinical outcomes.
抗氧化剂可中和活性氧和自由基，保护细胞免受氧化损伤并维持细胞内稳态。在癌症治疗中，它们发挥着复杂的双重作用，既是对抗氧化应激的保护剂，同时在某些条件下又作为促氧化剂，可能促进肿瘤发生和治疗抗性。氧化还原调节由关键的抗氧化途径（如BACH1和NRF2途径）以及显著影响癌症进展和免疫治疗反应的转录因子控制。除了其细胞内作用外，抗氧化剂还调节肿瘤微环境，包括与细胞外基质的相互作用，这会影响癌细胞行为和治疗反应。本综述还探讨了研究主要抗氧化剂在癌症生物学中作用的临床前研究。虽然这些研究提供了有前景的数据，但重大挑战依然存在，包括抗氧化剂可能干扰标准癌症治疗或无意中支持肿瘤存活的可能性。我们进一步强调了旨在优化抗氧化治疗的新兴策略，包括个性化医疗方法、基于纳米颗粒的递送系统以及与免疫疗法和靶向疗法的联合治疗。通过研究抗氧化剂的治疗潜力和相关风险，本综述提供了关于它们在癌症治疗中作用的关键见解，并为推进基于抗氧化剂的策略以改善临床结果提供了路线图。
