Zhao Lingyun, Guo Ruihong, Zhao Ziming, Wang Jue, Lou Zhonghan, Bao Jianfeng, Zheng Wei, Wang Qiang, Qiao Liang, Ye Yun, Kwan Hiu Yee, Zhou Hua, Wu Qibiao, Xu Keyang
Faculty of Chinese Medicine, and State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, 999078, China.
Chinese Medicine Guangdong Laboratory (Hengqin Laboratory), Guangdong-Macao In-Depth Cooperation Zone in Hengqin, Zhuhai, 519000, China.
Curr Oncol Rep. 2025 Apr 26. doi: 10.1007/s11912-025-01677-z.
Metabolic disorders significantly contribute to cancer burden globally. Uric acid (UA), a recognized metabolic risk factor linked to gout, also promotes insulin resistance, fatty liver, inflammation, and carcinogenesis. This systematic review evaluates UA's dual role in cancer, synthesizing epidemiological, mechanistic, and clinical evidence to clarify its potential as a therapeutic target.
The research of UA on cancer development mainly focuses on a clinical observational study, with limited molecular mechanism exploration. The associations between UA and cancer risk remain controversial, as sometimes the antioxidant, anti-inflammatory and immune-enhancing properties of UA are presented. There is lacking a systematic and updated review for summarizing the role of hyperuricemia on cancer risk and progression. The precise mechanism of UA in either enhancing or inhibiting cancer progression remains uncertain. Serum uric acid (SUA) exhibits paradoxical roles in cancer, with its effects varying by tumor type, concentration, gender, and disease stage. While UA predominantly drives tumorigenesis in most cancers, it shows protective effects in specific malignancies such as soft-tissue sarcoma and laryngeal squamous cell carcinoma, potentially through antioxidant activity at lower concentrations. Mechanistically, UA highly participate in the cancer risk and progression through reactive oxygen species (ROS) generation, disrupting T cell activation and dendritic cell maturation, exacerbating insulin resistance, and driving xanthine oxidoreductase (XOR) expression during the process of wound healing. Emerging clinical and mechanistic evidence highlights its oncogenic potential, underscoring the need for large-scale randomized controlled trials and cohort studies to clarify the relationship between hyperuricemia and cancer progression. Future research should prioritize exploring anti-UA therapies for cancer treatment, developing advanced animal models to dissect UA's mechanisms, and integrating diverse genomic datasets to unravel its context-dependent roles. Addressing these gaps will advance targeted strategies to leverage UA biology in cancer management.
代谢紊乱在全球范围内对癌症负担有显著影响。尿酸（UA）是一种与痛风相关的公认代谢风险因素，也会促进胰岛素抵抗、脂肪肝、炎症和致癌作用。本系统综述评估了UA在癌症中的双重作用，综合了流行病学、机制和临床证据，以阐明其作为治疗靶点的潜力。
关于UA对癌症发展的研究主要集中在临床观察性研究上，分子机制探索有限。UA与癌症风险之间的关联仍存在争议，因为有时会呈现出UA的抗氧化、抗炎和免疫增强特性。缺乏对高尿酸血症在癌症风险和进展中的作用进行系统和更新的综述。UA促进或抑制癌症进展的确切机制仍不确定。血清尿酸（SUA）在癌症中表现出矛盾的作用，其影响因肿瘤类型、浓度、性别和疾病阶段而异。虽然UA在大多数癌症中主要驱动肿瘤发生，但它在特定恶性肿瘤如软组织肉瘤和喉鳞状细胞癌中显示出保护作用，可能是通过较低浓度下的抗氧化活性。从机制上讲，UA通过产生活性氧（ROS）、破坏T细胞活化和树突状细胞成熟、加剧胰岛素抵抗以及在伤口愈合过程中驱动黄嘌呤氧化还原酶（XOR）表达，高度参与癌症风险和进展。新出现的临床和机制证据突出了其致癌潜力，强调需要进行大规模随机对照试验和队列研究，以阐明高尿酸血症与癌症进展之间的关系。未来的研究应优先探索针对癌症治疗的抗UA疗法，开发先进的动物模型以剖析UA的机制，并整合各种基因组数据集以揭示其依赖于背景的作用。填补这些空白将推进在癌症管理中利用UA生物学的靶向策略。
