{
  "abstract": "Lactate and its mediated modification, lactylation, are receiving increasing attention in the field of tumor biology. This review provides a comprehensive overview of the mechanistic involvement of lactate and lactylation in key oncogenic processes, such as tumor initiation, proliferation, invasion, metastasis, recurrence, and drug resistance. Rather than being a passive byproduct of glycolysis, lactate actively shapes the tumor microenvironment (TME), modulates immune responses, drives metabolic adaptation, and influences epigenetic and transcriptomic regulation. Lactylation, as a novel epigenetic mechanism, links cellular metabolism with gene expression by modifying histone and nonhistone proteins, thereby regulating chromatin accessibility, immune evasion, and DNA repair. Notably, this article proposes a new perspective: lactate accumulation in certain tumors may constitute an adaptive metabolic strategy rather than a passive consequence of altered metabolism. This paradigm challenges the traditional perception of lactate as a metabolic waste, instead proposing its dual function as both a signaling molecule and a strategic modulator of tumor progression. The interplay of lactate-mediated signaling pathways, such as the PI3K/AKT, Hippo, Wnt, MAPK, and JAK/STAT pathways, further underscores the role of lactate in cancer progression. This review also explores therapeutic opportunities targeting lactate metabolism and lactylation, including inhibitors of LDH, MCTs, and lactylation-modifying enzymes, as well as the synergistic potential of combining lactate-targeted approaches with chemotherapy, immunotherapy, and targeted therapy. Overall, this review provides an integrative overview of lactate-mediated mechanisms and highlights their potential as targets for metabolism-oriented therapeutic interventions in oncology.",
  "abstract_shown": true,
  "affiliations": [
    "Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Living Donor Liver Transplantation (Nanjing Medical University), Jiangsu Provincial Medical Innovation Center, Jiangsu Provincial Medical Key Laboratory, Nanjing, China",
    "Department of Medical Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China",
    "Department of Hepatobiliary Pancreatic Spleen Surgery, The Affiliated Hospital of Jiangsu University, Zhenjiang, China",
    "Department of Infectious Diseases, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China. daijingjing@njmu.edu.cn",
    "Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Living Donor Liver Transplantation (Nanjing Medical University), Jiangsu Provincial Medical Innovation Center, Jiangsu Provincial Medical Key Laboratory, Nanjing, China. liqingjsph@njmu.edu.cn",
    "Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China. wangxh@njmu.edu.cn",
    "Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Living Donor Liver Transplantation (Nanjing Medical University), Jiangsu Provincial Medical Innovation Center, Jiangsu Provincial Medical Key Laboratory, Nanjing, China. wangxh@njmu.edu.cn"
  ],
  "article_type": "review",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Chunyao Fang"
    },
    {
      "affs": [
        0
      ],
      "name": "Suiqing Zhou",
      "orcid": "0009-0002-3795-8039"
    },
    {
      "affs": [
        0
      ],
      "name": "Kai Yu"
    },
    {
      "affs": [
        0
      ],
      "name": "Liren Zhang",
      "orcid": "0009-0002-1649-0393"
    },
    {
      "affs": [
        1
      ],
      "name": "Wenxin Lian"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiaofeng Tie"
    },
    {
      "affs": [
        2
      ],
      "name": "Shu Chen"
    },
    {
      "affs": [
        3
      ],
      "name": "Jingjing Dai"
    },
    {
      "affs": [
        4
      ],
      "name": "Qing Hao Li"
    },
    {
      "affs": [
        5,
        6
      ],
      "name": "Xuehao Wang",
      "orcid": "0000-0001-5849-0098"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/8yjfjxpghm3zk.bib",
  "cited_by": 28,
  "doi": "10.1038/s41392-026-02672-x",
  "fulltext_url": null,
  "id": "8yjfjxpghm3zk",
  "issns": [
    "2059-3635",
    "2095-9907"
  ],
  "landing_url": "https://doi.org/10.1038/s41392-026-02672-x",
  "language": "en",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1306|Cancer, Hypoxia, and Metabolism"
    ]
  ],
  "openalex": "W7161800012",
  "pdf_url": "https://www.nature.com/articles/s41392-026-02672-x.pdf",
  "pmcid": "PMC13190781",
  "pmid": "42161914",
  "published": "2026-05-21",
  "publisher": "Springer Nature",
  "ris": "https://research.draconitic.com/paper/8yjfjxpghm3zk.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:26:46Z",
      "native_id": "W7161800012",
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      "url": "https://doi.org/10.1038/s41392-026-02672-x"
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  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:1306|Cancer, Hypoxia, and Metabolism",
      "subfield": "oncology"
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  ],
  "title": "Lactate metabolism and lactylation in cancer: from pathogenesis to therapeutic advances",
  "title_text": "Lactate metabolism and lactylation in cancer: from pathogenesis to therapeutic advances",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T13:21:05Z",
  "url": "https://research.draconitic.com/paper/8yjfjxpghm3zk",
  "venue": "Signal Transduction and Targeted Therapy",
  "versions": []
}