{"title":"Linking Hyperuricemia to Cancer: Emerging Evidence on Risk and Progression.","authors":"Lingyun Zhao, Ruihong Guo, Ziming Zhao, Jue Wang, Zhonghan Lou, Jianfeng Bao, Wei Zheng, Qiang Wang, Liang Qiao, Yun Ye, Hiu Yee Kwan, Hua Zhou, Qibiao Wu, Keyang Xu","doi":"10.1007/s11912-025-01677-z","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose of review: </strong>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.</p><p><strong>Recent findings: </strong>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.</p>","PeriodicalId":10861,"journal":{"name":"Current Oncology Reports","volume":" ","pages":"703-716"},"PeriodicalIF":5.0000,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current Oncology Reports","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s11912-025-01677-z","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/4/26 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Purpose of review: 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.
Recent findings: 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.
期刊介绍：
This journal aims to review the most important, recently published clinical findings in the field of oncology. By providing clear, insightful, balanced contributions by international experts, the journal intends to serve all those involved in the care of those affected by cancer.
We accomplish this aim by appointing international authorities to serve as Section Editors in key subject areas, such as cancer prevention, leukemia, melanoma, neuro-oncology, and palliative medicine. Section Editors, in turn, select topics for which leading experts contribute comprehensive review articles that emphasize new developments and recently published papers of major importance, highlighted by annotated reference lists. An international Editorial Board reviews the annual table of contents, suggests articles of special interest to their country/region, and ensures that topics are current and include emerging research. Commentaries from well-known figures in the field are also provided.
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