Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Oncology Letters
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-1074 Online ISSN: 1792-1082
Journal Cover
January-2026 Volume 31 Issue 1

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
January-2026 Volume 31 Issue 1

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Review Open Access

From mechanism to targeted therapy: Advances in histone lactylation‑driven cancer progression (Review)

  • Authors:
    • Zhe Jia
    • Shan Lu
    • Zhenchuan Wang
    • Pengfei Ge
  • View Affiliations / Copyright

    Affiliations: Department of Neurosurgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
    Copyright: © Jia et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 28
    |
    Published online on: November 11, 2025
       https://doi.org/10.3892/ol.2025.15381
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

As a novel lactate‑derived post‑translational modification, histone lactylation links metabolic reprogramming and epigenetic regulation in cancer. Histone lactylation, particularly at histone H3 lysine 18 lactylation (H3K18la), has been implicated in tumor initiation, progression, metastasis, immune evasion and therapy resistance. It modulates oncogenic pathways (such as PI3K/Akt/mTOR, NF‑κB, JAK/STAT) and metabolic pathways (such as glycolysis enhancement, fatty acid synthesis via stearoyl‑CoA desaturase and glutamine metabolism) and by altering chromatin structure and gene transcription. In the tumor microenvironment, lactate‑induced H3K18la polarizes macrophages toward an M2 phenotype, upregulates immune checkpoints and induces CD8+ T cells dysfunction, which promotes immunosuppression. However, CD8+ T cell‑intrinsic lactylation may enhance antitumor immunity during checkpoint blockade. Histone lactylation also induces chemoresistance via autophagy activation, DNA repair and ferroptosis suppression. Therapeutic strategies targeting lactylation include inhibiting lactate transporters, glycolysis or regulation enzymes (such as E1A‑binding protein, lysine acetyltransferase 2A and brahma‑related gene 1). Furthermore, the clinical potential is emerging, with H3K18la and H4K5la serving as prognostic biomarkers in multiple types of cancer. However, key questions regarding the non‑enzymatic modification mechanisms, identification of histone lactation regulatory enzymes and pan‑cancer functional heterogeneity are yet to be elucidated. Future research should prioritize translational validation of lactylation‑targeted therapies and their integration with existing regimens to overcome resistance and improve immunotherapy efficacy.
View Figures

Figure 1

Potential therapeutic strategies
targeting histone lactylation. Key strategies to modulate histone
lactylation include: i) Downregulating lactate flux (via MCT1/4
inhibition); ii) inhibition of the expression of glycolytic genes
(such as HK2, LDHA, ENO2, PFK, PKM2, PDK1 and
SLC2A1); iii) blocking lactylation-recognizing ‘readers’
(e.g., Brg1, DPF2, TRIM33) and modifying ‘writers’ (e.g., P300,
KAT2A, KAT5, KAT8, HBO1); and iv) enhancing the enzymatic activity
of ‘erasers’ (e.g., SIRT1-3, HDAC1-3). ‘T’ shaped arrows denote the
inhibitions of the pathways. DCA, sodium dichloroacetate; SLC2A1,
solute carrier family 2 member 1; MCT1, monocarboxylate transporter
1; MCT4, monocarboxylate transporter 4; HK2, hexokinase 2; LDHA,
lactate dehydrogenase; ENO2, enolase 2; PFK, phosphofructokinase;
PKM2, pyruvate kinase isozyme type M2; PDK1, pyruvate dehydrogenase
kinase 1; HBO1, home box office 1; La, lactate; Brg1,
brahma-related gene 1; DPF2, double PHD fingers 2; TRIM33,
tripartite motif containing 33; ASF1A, anti-silencing function 1A
histone chaperone; P300, E1A-binding protein; ACSS2, acyl-CoA
synthetase short chain family member 2; KAT, lysine
acetyltransferase; HDAC, histone deacetylase; SIRT, sirtuin.
View References

1 

Zhong Q, Xiao X, Qiu Y, Xu Z, Chen C, Chong B, Zhao X, Hai S, Li S, An Z and Dai L: Protein posttranslational modifications in health and diseases: Functions, regulatory mechanisms, and therapeutic implications. MedComm (2020). 4:e2612023. View Article : Google Scholar : PubMed/NCBI

2 

Lee JM, Hammaren HM, Savitski MM and Baek SH: Control of protein stability by Post-translational modifications. Nat Commun. 14:2012023. View Article : Google Scholar : PubMed/NCBI

3 

Shu F, Xiao H, Li QN, Ren XS, Liu ZG, Hu BW, Wang HS, Wang H and Jiang GM: Epigenetic and Post-translational modifications in autophagy: Biological functions and therapeutic targets. Signal Transduct Target Ther. 8:322023. View Article : Google Scholar : PubMed/NCBI

4 

Li Z, Chen J, Huang H, Zhan Q, Wang F, Chen Z, Lu X and Sun G: Post-translational modifications in diabetic cardiomyopathy. J Cell Mol Med. 28:e181582024. View Article : Google Scholar : PubMed/NCBI

5 

Winston DJ, Pakrasi A and Busuttil RW: Prophylactic fluconazole in liver transplant recipients. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 131:729–737. 1999. View Article : Google Scholar : PubMed/NCBI

6 

Durrant JD, de Oliveira CA and McCammon JA: POVME: An algorithm for measuring Binding-pocket volumes. J Mol Graph Model. 29:773–776. 2011. View Article : Google Scholar : PubMed/NCBI

7 

Silman I, Roth E, Paz A, Triquigneaux MM, Ehrenshaft M, Xu Y, Shnyrov VL, Sussman JL, Deterding LJ, Ashani Y, et al: The specific interaction of the photosensitizer methylene blue with acetylcholinesterase provides a model system for studying the molecular consequences of photodynamic therapy. Chem Biol Interact. 203:63–66. 2013. View Article : Google Scholar : PubMed/NCBI

8 

Hanson G and Coller J: Codon optimality, bias and usage in translation and mRNA decay. Nat Rev Mol Cell Biol. 19:20–30. 2018. View Article : Google Scholar : PubMed/NCBI

9 

Jenuwein T and Allis CD: Translating the histone code. Science. 293:1074–1080. 2001. View Article : Google Scholar : PubMed/NCBI

10 

Mansour MR, Abraham BJ, Anders L, Berezovskaya A, Gutierrez A, Durbin AD, Etchin J, Lawton L, Sallan SE, Silverman LB, et al: Oncogene regulation. An oncogenic super-enhancer formed through somatic mutation of a noncoding intergenic element. Science. 346:1373–1377. 2014. View Article : Google Scholar : PubMed/NCBI

11 

Liu XY, Guo CH, Xi ZY, Xu XQ, Zhao QY, Li LS and Wang Y: Histone methylation in pancreatic cancer and its clinical implications. World J Gastroenterol. 27:6004–6024. 2021. View Article : Google Scholar : PubMed/NCBI

12 

Komar D and Juszczynski P: Rebelled epigenome: Histone H3S10 phosphorylation and H3S10 kinases in cancer biology and therapy. Clin Epigenetics. 12:1472020. View Article : Google Scholar : PubMed/NCBI

13 

Tamburri S, Conway E and Pasini D: Polycomb-dependent histone H2A ubiquitination links developmental disorders with cancer. Trends Genet. 38:333–352. 2022. View Article : Google Scholar : PubMed/NCBI

14 

Duan X, Xing Z, Qiao L, Qin S, Zhao X, Gong Y and Li X: The role of histone post-translational modifications in cancer and cancer immunity: Functions, mechanisms and therapeutic implications. Front Immunol. 15:14952212024. View Article : Google Scholar : PubMed/NCBI

15 

Li X, Yang Y, Zhang B, Lin X, Fu X, An Y, Zou Y, Wang JX, Wang Z and Yu T: Lactate metabolism in human health and disease. Signal Transduct Target Ther. 7:3052022. View Article : Google Scholar : PubMed/NCBI

16 

Zhao Y and Hong J: Purification of recombinant histones and mononucleosome assembly. Curr Protoc. 5:e701552025. View Article : Google Scholar : PubMed/NCBI

17 

Zhang D, Tang Z, Huang H, Zhou G, Cui C, Weng Y, Liu W, Kim S, Lee S, Perez-Neut M, et al: Metabolic regulation of gene expression by histone lactylation. Nature. 574:575–580. 2019. View Article : Google Scholar : PubMed/NCBI

18 

Hu Y, He Z, Li Z, Wang Y, Wu N, Sun H, Zhou Z, Hu Q and Cong X: Lactylation: The novel histone modification influence on gene expression, protein function, and disease. Clin Epigenetics. 16:722024. View Article : Google Scholar : PubMed/NCBI

19 

Yu X, Yang J, Xu J, Pan H, Wang W, Yu X and Shi S: Histone lactylation: From tumor lactate metabolism to epigenetic regulation. Int J Biol Sci. 20:1833–1854. 2024. View Article : Google Scholar : PubMed/NCBI

20 

Hou J, Guo M, Li Y and Liao Y: Lactylated histone H3K18 as a potential biomarker for the diagnosis and prediction of the severity of pancreatic cancer. Clinics (Sao Paulo). 80:1005442025. View Article : Google Scholar : PubMed/NCBI

21 

Li XM, Yang Y, Jiang FQ, Hu G, Wan S, Yan WY, He XS, Xiao F, Yang XM, Guo X, et al: Histone lactylation inhibits RARgamma expression in macrophages to promote colorectal tumorigenesis through activation of TRAF6-IL-6-STAT3 signaling. Cell Rep. 43:1136882024. View Article : Google Scholar : PubMed/NCBI

22 

Jin Z, Yun L and Cheng P: Tanshinone I reprograms glycolysis metabolism to regulate histone H3 lysine 18 lactylation (H3K18la) and inhibits cancer cell growth in ovarian cancer. Int J Biol Macromol. 291:1390722025. View Article : Google Scholar : PubMed/NCBI

23 

Guo Z, Tang Y, Wang S, Huang Y, Chi Q, Xu K and Xue L: Natural product fargesin interferes with H3 histone lactylation via targeting PKM2 to inhibit non-small cell lung cancer tumorigenesis. Biofactors. 50:592–607. 2024. View Article : Google Scholar : PubMed/NCBI

24 

Rabinowitz JD and Enerback S: Lactate: The ugly duckling of energy metabolism. Nat Metabo. 2:566–571. 2020. View Article : Google Scholar

25 

Chen S, Xu Y, Zhuo W and Zhang L: The emerging role of lactate in tumor microenvironment and its clinical relevance. Cancer Lett. 590:2168372024. View Article : Google Scholar : PubMed/NCBI

26 

Gatenby RA and Gillies RJ: Why do cancers have high aerobic glycolysis? Nat Rev Cancer. 4:891–899. 2004. View Article : Google Scholar : PubMed/NCBI

27 

Brooks GA, Osmond AD, Arevalo JA, Duong JJ, Curl CC, Moreno-Santillan DD and Leija RG: Lactate as a myokine and exerkine: Drivers and signals of physiology and metabolism. J Appl Physiol (1985). 134:529–548. 2023. View Article : Google Scholar : PubMed/NCBI

28 

Fang Y, Li Z, Yang L, Li W, Wang Y, Kong Z, Miao J, Chen Y, Bian Y and Zeng L: Emerging roles of lactate in acute and chronic inflammation. Cell Commun Signal. 22:2762024. View Article : Google Scholar : PubMed/NCBI

29 

Chang X, Zhou S, Liu J, Wang Y, Guan X, Wu Q, Liu Z and Liu R: Zishenhuoxue decoction-induced myocardial protection against ischemic injury through TMBIM6-VDAC1-mediated regulation of calcium homeostasis and mitochondrial quality surveillance. Phytomedicine. 132:1553312024. View Article : Google Scholar : PubMed/NCBI

30 

Chang X, Zhang Q, Huang Y, Liu J, Wang Y, Guan X, Wu Q, Liu Z and Liu R: Quercetin inhibits necroptosis in cardiomyocytes after ischemia-reperfusion via DNA-PKcs-SIRT5-orchestrated mitochondrial quality control. Phytother Res. 38:2496–2517. 2024. View Article : Google Scholar : PubMed/NCBI

31 

Nedel WL and Portela LV: Lactate levels in sepsis: Don't forget the mitochondria. Intensive Care Med. 50:1202–1203. 2024. View Article : Google Scholar : PubMed/NCBI

32 

Paul S, Ghosh S and Kumar S: Tumor glycolysis, an essential sweet tooth of tumor cells. Semin Cancer Biol. 86:1216–1230. 2022. View Article : Google Scholar : PubMed/NCBI

33 

Pandkar MR, Sinha S, Samaiya A and Shukla S: Oncometabolite lactate enhances breast cancer progression by orchestrating histone lactylation-dependent c-Myc expression. Transl Oncol. 37:1017582023. View Article : Google Scholar : PubMed/NCBI

34 

Ma F and Yu W: The roles of lactate and lactylation in diseases related to mitochondrial dysfunction. Int J Mol Sci. 26:71492025. View Article : Google Scholar : PubMed/NCBI

35 

Wang Y and Patti GJ: The Warburg effect: A signature of mitochondrial overload. Trends Cell Biol. 33:1014–1020. 2023. View Article : Google Scholar : PubMed/NCBI

36 

Shechter D, Dormann HL, Allis CD and Hake SB: Extraction, purification and analysis of histones. Nat Protoc. 2:1445–1457. 2007. View Article : Google Scholar : PubMed/NCBI

37 

Doenecke D, Albig W, Bode C, Drabent B, Franke K, Gavenis K and Witt O: Histones: Genetic diversity and Tissue-specific gene expression. Histochem Cell Biol. 107:1–10. 1997. View Article : Google Scholar : PubMed/NCBI

38 

Crane-Robinson C: Linker histones: History and current perspectives. Biochim Biophys Acta. 1859:431–435. 2016. View Article : Google Scholar : PubMed/NCBI

39 

Xu K, Zhang K, Wang Y and Gu Y: Comprehensive review of histone lactylation: Structure, function, and therapeutic targets. Biochem Pharmacol. 225:1163312024. View Article : Google Scholar : PubMed/NCBI

40 

Li H, Sun L, Gao P and Hu H: Lactylation in cancer: Current understanding and challenges. Cancer Cell. 42:1803–1807. 2024. View Article : Google Scholar : PubMed/NCBI

41 

Zhou JM, Dai WX, Wang RJ, Xu WQ, Xiang Z, Wang YX, Zhang T, Zhao YM, Wang L and Mao AR: Organoid modeling identifies USP3-AS1 as a novel promoter in colorectal cancer liver metastasis through increasing glucose-driven histone lactylation. Acta Pharmacol Sinica. 46:1404–1418. 2025. View Article : Google Scholar : PubMed/NCBI

42 

Wei S, Zhang J, Zhao R, Shi R, An L, Yu Z, Zhang Q, Zhang J, Yao Y, Li H and Wang H: Histone lactylation promotes malignant progression by facilitating USP39 expression to target PI3K/AKT/HIF-1α signal pathway in endometrial carcinoma. Cell Death Discov. 10:1212024. View Article : Google Scholar : PubMed/NCBI

43 

Yu J, Chai P, Xie M, Ge S, Ruan J, Fan X and Jia R: Histone lactylation drives oncogenesis by facilitating m6A reader protein YTHDF2 expression in ocular melanoma. Genome Biol. 22:852021. View Article : Google Scholar : PubMed/NCBI

44 

Gu X, Zhuang A, Yu J, Yang L, Ge S, Ruan J, Jia R, Fan X and Chai P: Histone lactylation-boosted ALKBH3 potentiates tumor progression and diminished promyelocytic leukemia protein nuclear condensates by m1A demethylation of SP100A. Nucleic Acids Res. 52:2273–2289. 2024. View Article : Google Scholar : PubMed/NCBI

45 

Du W, Tan S, Peng Y, Lin S, Wu Y, Ding K, Chen C, Liu R, Cao Y, Li Z, et al: Histone Lactylation-driven YTHDC1 promotes hepatocellular carcinoma progression via lipid metabolism remodeling. Cancer Lett. 611:2174262024. View Article : Google Scholar : PubMed/NCBI

46 

Li L, Li Z, Meng X, Wang X, Song D, Liu Y, Xu T, Qin J, Sun N, Tian K, et al: Histone lactylation-derived LINC01127 promotes the self-renewal of glioblastoma stem cells via the cis-regulating the MAP4K4 to activate JNK pathway. Cancer Lett. 579:2164672023. View Article : Google Scholar : PubMed/NCBI

47 

Wang J, Zhuang H, Yang X, Guo Z, Zhou K, Liu N, An Y, Chen Y, Zhang Z, Wang M, et al: Exploring the mechanism of ferroptosis induction by sappanone A in cancer: Insights into the mitochondrial dysfunction mediated by NRF2/xCT/GPX4 axis. Int J Biol Sci. 20:5145–5161. 2024. View Article : Google Scholar : PubMed/NCBI

48 

Pu X, Zhang Q, Liu J, Wang Y, Guan X, Wu Q, Liu Z, Liu R and Chang X: Ginsenoside Rb1 ameliorates heart failure through DUSP-1-TMBIM-6-mediated mitochondrial quality control and gut flora interactions. Phytomedicine. 132:1558802024. View Article : Google Scholar : PubMed/NCBI

49 

Pang B, Dong G, Pang T, Sun X, Liu X, Nie Y and Chang X: Emerging insights into the pathogenesis and therapeutic strategies for vascular endothelial injury-associated diseases: Focus on mitochondrial dysfunction. Angiogenesis. 27:623–639. 2024. View Article : Google Scholar : PubMed/NCBI

50 

Kenny TC and Birsoy K: Mitochondria and cancer. Cold Spring Harb Perspect Med. 14:a0415342024. View Article : Google Scholar : PubMed/NCBI

51 

Liu Y, Sun Y, Guo Y, Shi X, Chen X, Feng W, Wu LL, Zhang J, Yu S, Wang Y and Shi Y: An overview: The diversified role of mitochondria in cancer metabolism. Int J Biol Sci. 19:897–915. 2023. View Article : Google Scholar : PubMed/NCBI

52 

Lv M, Yang X, Xu C, Song Q, Zhao H, Sun T, Liu J, Zhang Y, Sun G, Xue Y and Zhang Z: SIRT4 promotes pancreatic cancer stemness by enhancing histone lactylation and epigenetic reprogramming stimulated by calcium signaling. Adv Sci (Weinh). 12:e24125532025. View Article : Google Scholar : PubMed/NCBI

53 

Chang X, Li Y, Liu J, Wang Y, Guan X, Wu Q, Zhou Y, Zhang X, Chen Y, Huang Y and Liu R: ß-tubulin contributes to Tongyang Huoxue decoction-induced protection against hypoxia/reoxygenation-induced injury of sinoatrial node cells through SIRT1-mediated regulation of mitochondrial quality surveillance. Phytomedicine. 108:1545022023. View Article : Google Scholar : PubMed/NCBI

54 

Chang X, Liu R, Li R, Peng Y, Zhu P and Zhou H: Molecular mechanisms of mitochondrial quality control in ischemic cardiomyopathy. Int J Biol Sci. 19:426–448. 2023. View Article : Google Scholar : PubMed/NCBI

55 

He Y, Ji Z, Gong Y, Fan L, Xu P, Chen X, Miao J, Zhang K, Zhang W, Ma P, et al: Numb/Parkin-directed mitochondrial fitness governs cancer cell fate via metabolic regulation of histone lactylation. Cell Rep. 42:1120332023. View Article : Google Scholar : PubMed/NCBI

56 

Wang H, Xu M, Zhang T, Pan J, Li C, Pan B, Zhou L, Huang Y, Gao C, He M, et al: PYCR1 promotes liver cancer cell growth and metastasis by regulating IRS1 expression through lactylation modification. Clin Transl Med. 14:e700452024. View Article : Google Scholar : PubMed/NCBI

57 

Deng J and Liao X: Lysine lactylation (Kla) might be a novel therapeutic target for breast cancer. BMC Med Genomics. 16:2832023. View Article : Google Scholar : PubMed/NCBI

58 

Liu M, Gu L, Zhang Y, Li Y, Zhang L, Xin Y, Wang Y and Xu ZX: LKB1 inhibits telomerase activity resulting in cellular senescence through histone lactylation in lung adenocarcinoma. Cancer Lett. 595:2170252024. View Article : Google Scholar : PubMed/NCBI

59 

Cui Z, Li Y, Lin Y, Zheng C, Luo L, Hu D, Chen Y, Xiao Z and Sun Y: Lactylproteome analysis indicates histone H4K12 lactylation as a novel biomarker in triple-negative breast cancer. Front Endocrinol (Lausanne). 15:13286792024. View Article : Google Scholar : PubMed/NCBI

60 

Li J, Chen Z, Jin M, Gu X, Wang Y, Huang G, Zhao W and Lu C: Histone H4K12 lactylation promotes malignancy progression in triple-negative breast cancer through SLFN5 downregulation. Cell Signal. 124:1114682024. View Article : Google Scholar : PubMed/NCBI

61 

Zang Y, Wang A, Zhang J, Xia M, Jiang Z, Jia B, Lu C, Chen C, Wang S, Zhang Y, et al: Hypoxia promotes histone H3K9 lactylation to enhance LAMC2 transcription in esophageal squamous cell carcinoma. iScience. 27:1101882024. View Article : Google Scholar : PubMed/NCBI

62 

Yang Y, Wen J, Lou S, Han Y, Pan Y, Zhong Y, He Q, Zhang Y, Mo X, Ma J and Shen N: DNAJC12 downregulation induces neuroblastoma progression via increased histone H4K5 lactylation. J Mol Cell Biol. 16:mjae0562025. View Article : Google Scholar : PubMed/NCBI

63 

Deng X, Huang Y, Zhang J, Chen Y, Jiang F, Zhang Z, Li T, Hou L, Tan W and Li F: Histone lactylation regulates PRKN-Mediated mitophagy to promote M2 Macrophage polarization in bladder cancer. Int Immunopharmacol. 148:1141192025. View Article : Google Scholar : PubMed/NCBI

64 

Li M, Sun P, Tu B, Deng G, Li D and He W: Hypoxia conduces the glioma progression by inducing M2 macrophage polarization via elevating TNFSF9 level in a Histone-lactylation-dependent manner. Am J Physiol Cell Physiol. 327:C487–C504. 2024. View Article : Google Scholar : PubMed/NCBI

65 

Cai J, Zhang P, Cai Y, Zhu G, Chen S, Song L, Du J, Wang B, Dai W, Zhou J, et al: Lactylation-Driven NUPR1 promotes immunosuppression of Tumor-infiltrating macrophages in hepatocellular carcinoma. Adv Sci (Weinh). 12:e24130952025. View Article : Google Scholar : PubMed/NCBI

66 

Yang J and Yu X, Xiao M, Xu H, Tan Z, Lei Y, Guo Y, Wang W, Xu J, Shi S and Yu X: Histone lactylation-driven feedback loop modulates cholesterol-linked immunosuppression in pancreatic cancer. Gut. 74:1859–1872. 2025. View Article : Google Scholar : PubMed/NCBI

67 

Chaudagar K, Hieromnimon HM, Kelley A, Labadie B, Shafran J, Rameshbabu S, Drovetsky C, Bynoe K, Solanki A, Markiewicz E, et al: Suppression of tumor cell lactate-generating signaling pathways eradicates murine PTEN/p53-deficient Aggressive-variant prostate cancer via macrophage phagocytosis. Clin Cancer Res. 29:4930–4940. 2023. View Article : Google Scholar : PubMed/NCBI

68 

Xiong J, He J, Zhu J, Pan J, Liao W, Ye H, Wang H, Song Y, Du Y, Cui B, et al: Lactylation-driven METTL3-mediated RNA m6A modification promotes immunosuppression of tumor-infiltrating myeloid cells. Mol Cell. 82:1660–1677.e10. 2022. View Article : Google Scholar : PubMed/NCBI

69 

Yamamoto Y, Kasashima H, Fukui Y, Tsujio G, Yashiro M and Maeda K: The heterogeneity of cancer-associated fibroblast subpopulations: Their origins, biomarkers, and roles in the tumor microenvironment. Cancer Sci. 114:16–24. 2023. View Article : Google Scholar : PubMed/NCBI

70 

Zhang C, Zhou W, Xu H, Xu J, Li J, Liu X, Lu X, Dai J, Jiang Y, Wang W, et al: Cancer-associated fibroblasts promote EGFR-TKI resistance via the CTHRC1/glycolysis/H3K18la positive feedback loop. Oncogene. 44:1400–1414. 2025. View Article : Google Scholar : PubMed/NCBI

71 

Zhou J, Xu W, Wu Y, Wang M, Zhang N, Wang L, Feng Y, Zhang T, Wang L and Mao A: GPR37 promotes colorectal cancer liver metastases by enhancing the glycolysis and histone lactylation via hippo pathway. Oncogene. 42:3319–3330. 2023. View Article : Google Scholar : PubMed/NCBI

72 

Ugolini A, De Leo A, Yu X, Scirocchi F, Liu X, Peixoto B, Scocozza D, Pace A, Perego M, Gardini A, et al: Functional reprogramming of neutrophils within the brain tumor microenvironment by Hypoxia-driven histone lactylation. Cancer Discov. 15:1270–1296. 2025. View Article : Google Scholar : PubMed/NCBI

73 

Wang R, Li C, Cheng Z, Li M, Shi J, Zhang Z, Jin S and Ma H: H3K9 lactylation in malignant cells facilitates CD8(+) T cell dysfunction and poor immunotherapy response. Cell Rep. 43:1146862024. View Article : Google Scholar : PubMed/NCBI

74 

Raychaudhuri D, Singh P, Chakraborty B, Hennessey M, Tannir AJ, Byregowda S, Natarajan SM, Trujillo-Ocampo A, Im JS and Goswami S: Histone lactylation drives CD8+ T cell metabolism and function. Nat Immunol. 25:2140–2151. 2024. View Article : Google Scholar : PubMed/NCBI

75 

Li W, Zhou C, Yu L, Hou Z, Liu H, Kong L, Xu Y, He J, Lan J, Ou Q, et al: Tumor-derived lactate promotes resistance to bevacizumab treatment by facilitating autophagy enhancer protein RUBCNL expression through histone H3 lysine 18 lactylation (H3K18la) in colorectal cancer. Autophagy. 20:114–130. 2024. View Article : Google Scholar : PubMed/NCBI

76 

Li F, Zhang H, Huang Y, Li D, Zheng Z, Xie K, Cao C, Wang Q, Zhao X, Huang Z, et al: Single-cell transcriptome analysis reveals the association between histone lactylation and cisplatin resistance in bladder cancer. Drug Resist Updat. 73:1010592024. View Article : Google Scholar : PubMed/NCBI

77 

Dong R, Fei Y, He Y, Gao P, Zhang B, Zhu M, Wang Z, Wu L, Wu S, Wang X, et al: Lactylation-driven HECTD2 limits the response of hepatocellular carcinoma to lenvatinib. Adv Sci (Weinh). 12:e24125592025. View Article : Google Scholar : PubMed/NCBI

78 

Zeng Y, Jiang H, Chen Z, Xu J, Zhang X, Cai W, Zeng X, Ma P, Lin R, Yu H, et al: Histone lactylation promotes multidrug resistance in hepatocellular carcinoma by forming a positive feedback loop with PTEN. Cell Death Dis. 16:592025. View Article : Google Scholar : PubMed/NCBI

79 

Wang ZC, Li C, Zhang Z, Lu S, Liu YM, Qi P, Chen X, Wang YB, Feng WJ, Pan CL, et al: Targeting PPARα activation sensitizes glioblastoma cells to temozolomide and reverses acquired resistance by inhibiting H3K18 lactylation. Acta Pharmacol Sin. 46:3071–3086. 2025. View Article : Google Scholar : PubMed/NCBI

80 

Chen Z, Zhang Y, Yan F, Zhao G and Wang Y: tsRNA-08614 inhibits glycolysis and histone lactylation by ALDH1A3 to confer oxaliplatin sensitivity in colorectal cancer. Transl Oncol. 58:1024272025. View Article : Google Scholar : PubMed/NCBI

81 

Deng J, Li Y, Yin L, Liu S, Li Y, Liao W, Mu L, Luo X and Qin J: Histone lactylation enhances GCLC expression and thus promotes chemoresistance of colorectal cancer stem cells through inhibiting ferroptosis. Cell Death Dis. 16:1932025. View Article : Google Scholar : PubMed/NCBI

82 

Zhang K, Guo L, Li X, Hu Y and Luo N: Cancer-associated fibroblasts promote doxorubicin resistance in triple-negative breast cancer through enhancing ZFP64 histone lactylation to regulate ferroptosis. J Transl Med. 23:2472025. View Article : Google Scholar : PubMed/NCBI

83 

Duan W, Liu W, Xia S, Zhou Y, Tang M, Xu M, Lin M, Li X and Wang Q: Warburg effect enhanced by AKR1B10 promotes acquired resistance to pemetrexed in lung cancer-derived brain metastasis. J Transl Med. 21:5472023. View Article : Google Scholar : PubMed/NCBI

84 

Lu B, Chen S, Guan X, Chen X, Du Y, Yuan J, Wang J, Wu Q, Zhou L, Huang X and Zhao Y: Lactate accumulation induces H4K12la to activate super-enhancer-driven RAD23A expression and promote niraparib resistance in ovarian cancer. Mol Cancer. 24:832025. View Article : Google Scholar : PubMed/NCBI

85 

Sun C, Li X, Teng Q, Liu X, Song L, Schiöth HB, Wu H, Ma X, Zhang Z, Qi C, et al: Targeting platinum-resistant ovarian cancer by disrupting histone and RAD51 lactylation. Theranostics. 15:3055–3075. 2025. View Article : Google Scholar : PubMed/NCBI

86 

Yue Q, Wang Z, Shen Y, Lan Y, Zhong X, Luo X, Yang T, Zhang M, Zuo B, Zeng T, et al: Histone H3K9 lactylation confers temozolomide resistance in glioblastoma via luc7l2-mediated MLH1 intron retention. Adv Sci (Weinh). 11:e23092902024. View Article : Google Scholar : PubMed/NCBI

87 

Ling SP, Ming LC, Dhaliwal JS, Gupta M, Ardianto C, Goh KW, Hussain Z and Shafqat N: Role of immunotherapy in the treatment of cancer: A systematic review. Cancers (Basel). 14:52052022. View Article : Google Scholar : PubMed/NCBI

88 

Arafat Hossain M: A comprehensive review of immune checkpoint inhibitors for cancer treatment. Int Immunopharmacol. 143:1133652024. View Article : Google Scholar : PubMed/NCBI

89 

Zhang C, Zhou L, Zhang M, Du Y, Li C, Ren H and Zheng L: H3K18 lactylation potentiates immune escape of Non-small cell lung cancer. Cancer Res. 84:3589–3601. 2024. View Article : Google Scholar : PubMed/NCBI

90 

Huang ZW, Zhang XN, Zhang L, Liu LL, Zhang JW, Sun YX, Xu JQ, Liu Q and Long ZJ: STAT5 promotes PD-L1 expression by facilitating histone lactylation to drive immunosuppression in acute myeloid leukemia. Signal Transduct Target Ther. 8:3912023. View Article : Google Scholar : PubMed/NCBI

91 

Li Z, Liang P, Chen Z, Chen Z, Jin T, He F, Chen X and Yang K: CAF-secreted LOX promotes PD-L1 expression via histone Lactylation and regulates tumor EMT through TGFβ/IGF1 signaling in gastric cancer. Cell Signal. 124:1114622024. View Article : Google Scholar : PubMed/NCBI

92 

Chao J, Chen GD, Huang ST, Gu H, Liu YY, Luo Y, Lin Z, Chen ZZ, Li X, Zhang B, et al: High histone H3K18 lactylation level is correlated with poor prognosis in epithelial ovarian cancer. Neoplasma. 71:319–332. 2024. View Article : Google Scholar : PubMed/NCBI

93 

Hu X, Huang Z and Li L: LDHB mediates histone lactylation to activate PD-L1 and promote ovarian cancer immune escape. Cancer Invest. 43:70–79. 2025. View Article : Google Scholar : PubMed/NCBI

94 

Ding CH, Yan FZ, Xu BN, Qian H, Hong XL, Liu SQ, Luo YY, Wu SH, Cai LY, Zhang X and Xie WF: PRMT3 drives PD-L1-mediated immune escape through activating PDHK1-regulated glycolysis in hepatocellular carcinoma. Cell Death Dis. 16:1582025. View Article : Google Scholar : PubMed/NCBI

95 

Ma Z, Yang J, Jia W, Li L, Li Y, Hu J, Luo W, Li R, Ye D and Lan P: Histone Lactylation-driven B7-H3 expression promotes tumor immune evasion. Theranostics. 15:2338–2359. 2025. View Article : Google Scholar : PubMed/NCBI

96 

Jia X, Yan B, Tian X, Liu Q, Jin J, Shi J and Hou Y: CD47/SIRPα pathway mediates cancer immune escape and immunotherapy. Int J Biol Sci. 17:3281–3287. 2021. View Article : Google Scholar : PubMed/NCBI

97 

Liu Y, Weng L, Wang Y, Zhang J, Wu Q, Zhao P, Shi Y, Wang P and Fang L: Deciphering the role of CD47 in cancer immunotherapy. J Adv Res. 63:129–158. 2024. View Article : Google Scholar : PubMed/NCBI

98 

Wang S, Huang T, Wu Q, Yuan H, Wu X, Yuan F, Duan T, Taori S, Zhao Y, Snyder NW, et al: Lactate reprograms glioblastoma immunity through CBX3-regulated histone lactylation. J Clin Invest. 134:e1768512024. View Article : Google Scholar : PubMed/NCBI

99 

Zhu Y, Fu Y, Liu F, Yan S and Yu R: Appraising histone H4 lysine 5 lactylation as a novel biomarker in breast cancer. Sci Rep. 15:82052025. View Article : Google Scholar : PubMed/NCBI

100 

Wu Q, Li X, Long M, Xie X and Liu Q: Integrated analysis of histone lysine lactylation (Kla)-specific genes suggests that NR6A1, OSBP2 and UNC119B are novel therapeutic targets for hepatocellular carcinoma. Sci Rep. 13:186422023. View Article : Google Scholar : PubMed/NCBI

101 

He W, Chen R, Chen G, Zhang L, Qian Y, Zhou J, Peng J, Wong VKW and Jiang Y: Identification and validation of prognostic genes related to histone lactylation modification in Glioblastoma: An integrated analysis of transcriptome and Single-cell RNA sequencing. J Cancer. 16:2145–2166. 2025. View Article : Google Scholar : PubMed/NCBI

102 

Zhang H, Yang X, Xue Y, Huang Y, Mo Y, Huang Y, Zhang H, Zhang X, Zhao W, Jia B, et al: A basigin antibody modulates MCTs to impact tumor metabolism and immunity. Cell Discov. 11:442025. View Article : Google Scholar : PubMed/NCBI

103 

Silva A, Antunes B, Batista A, Pinto-Ribeiro F, Baltazar F and Afonso J: In vivo anticancer activity of AZD3965: A systematic review. Molecules. 27:1812021. View Article : Google Scholar : PubMed/NCBI

104 

Chen J, Huang Z, Chen Y, Tian H, Chai P, Shen Y, Yao Y, Xu S, Ge S and Jia R: Lactate and lactylation in cancer. Signal Transduct Target Ther. 10:382025. View Article : Google Scholar : PubMed/NCBI

105 

Zhang Q, Cao L and Xu K: Role and mechanism of lactylation in cancer. Zhongguo Fei Ai Za Zhi. 27:471–479. 2024.(In Chinese). PubMed/NCBI

106 

Yao W, Hu X and Wang X: Crossing epigenetic frontiers: The intersection of novel histone modifications and diseases. Signal Transduct Target Ther. 9:2322024. View Article : Google Scholar : PubMed/NCBI

107 

Sharma D, Singh M and Rani R: Role of LDH in tumor glycolysis: Regulation of LDHA by small molecules for cancer therapeutics. Semin Cancer Biol. 87:184–195. 2022. View Article : Google Scholar : PubMed/NCBI

108 

Hu X, Huang X, Yang Y, Sun Y, Zhao Y, Zhang Z, Qiu D, Wu Y, Wu G and Lei L: Dux activates metabolism-lactylation-MET network during early iPSC reprogramming with Brg1 as the histone lactylation reader. Nucleic Acids Res. 52:5529–5548. 2024. View Article : Google Scholar : PubMed/NCBI

109 

Fan Z, Liu Z, Zhang N, Wei W, Cheng K, Sun H and Hao Q: Identification of SIRT3 as an eraser of H4K16la. iScience. 26:1077572023. View Article : Google Scholar : PubMed/NCBI

110 

Moreno-Yruela C, Zhang D, Wei W, Bæk M, Liu W, Gao J, Danková D, Nielsen AL, Bolding JE, Yang L, et al: Class I histone deacetylases (HDAC1-3) are histone lysine delactylases. Sci Adv. 8:eabi66962022. View Article : Google Scholar : PubMed/NCBI

111 

Qin Q, Wang D, Qu Y, Li J, An K, Mao Z, Li J, Xiong Y, Min Z and Xue Z: Enhanced glycolysis-derived lactate promotes microglial activation in Parkinson's disease via histone lactylation. NPJ Parkinsons Dis. 11:32025. View Article : Google Scholar : PubMed/NCBI

112 

Wang N, Wang W, Wang X, Mang G, Chen J, Yan X, Tong Z, Yang Q, Wang M, Chen L, et al: Histone lactylation boosts reparative gene activation Post-myocardial infarction. Circ Res. 131:893–908. 2022. View Article : Google Scholar : PubMed/NCBI

113 

Zhu R, Ye X, Lu X, Xiao L, Yuan M, Zhao H, Guo D, Meng Y, Han H, Luo S, et al: ACSS2 acts as a lactyl-CoA synthetase and couples KAT2A to function as a lactyltransferase for histone lactylation and tumor immune evasion. Cell Metab. 37:361–376.e7. 2025. View Article : Google Scholar : PubMed/NCBI

114 

Niu Z, Chen C, Wang S, Lu C, Wu Z, Wang A, Mo J, Zhang J, Han Y, Yuan Y, et al: HBO1 catalyzes lysine lactylation and mediates histone H3K9la to regulate gene transcription. Nat Commun. 15:35612024. View Article : Google Scholar : PubMed/NCBI

115 

Zou Y, Cao M, Tai M, Zhou H, Tao L, Wu S, Yang K, Zhang Y, Ge Y, Wang H, et al: A Feedback loop driven by H4K12 lactylation and HDAC3 in macrophages regulates Lactate-induced collagen synthesis in fibroblasts via the TGF-β signaling. Adv Sci (Weinh). 12:e24114082025. View Article : Google Scholar : PubMed/NCBI

116 

Dong M, Zhang Y, Chen M, Tan Y, Min J, He X, Liu F, Gu J, Jiang H, Zheng L, et al: ASF1A-dependent P300-mediated histone H3 lysine 18 lactylation promotes atherosclerosis by regulating EndMT. Acta Pharm Sin B. 14:3027–3048. 2024. View Article : Google Scholar : PubMed/NCBI

117 

Sun Y, Sun Y, Yue S, Wang Y and Lu F: Histone deacetylase inhibitors in cancer therapy. Curr Top Med Chem. 18:2420–2428. 2018. View Article : Google Scholar : PubMed/NCBI

118 

Li F, Si W, Xia L, Yin D, Wei T, Tao M, Cui X, Yang J, Hong T and Wei R: Positive feedback regulation between glycolysis and histone lactylation drives oncogenesis in pancreatic ductal adenocarcinoma. Mol Cancer. 23:902024. View Article : Google Scholar : PubMed/NCBI

119 

Du R, Gao Y, Yan C, Ren X, Qi S, Liu G, Guo X, Song X, Wang H, Rao J, et al: Sirtuin 1/sirtuin 3 are robust lysine delactylases and sirtuin 1-mediated delactylation regulates glycolysis. iScience. 27:1109112024. View Article : Google Scholar : PubMed/NCBI

120 

Zu H, Li C, Dai C, Pan Y, Ding C, Sun H, Zhang X, Yao X, Zang J and Mo X: SIRT2 functions as a histone delactylase and inhibits the proliferation and migration of neuroblastoma cells. Cell Discov. 8:542022. View Article : Google Scholar : PubMed/NCBI

121 

Xu Y, Meng W, Dai Y, Xu L, Ding N, Zhang J and Zhuang X: Anaerobic metabolism promotes breast cancer survival via Histone-3 Lysine-18 lactylation mediating PPARD axis. Cell Death Discov. 11:542025. View Article : Google Scholar : PubMed/NCBI

122 

Tsukihara S, Akiyama Y, Shimada S, Hatano M, Igarashi Y, Taniai T, Tanji Y, Kodera K, Yasukawa K, Umeura K, et al: Delactylase effects of SIRT1 on a positive feedback loop involving the H19-glycolysis-histone lactylation in gastric cancer. Oncogene. 44:724–738. 2025. View Article : Google Scholar : PubMed/NCBI

123 

Chen C, Zhang Y, Zang Y, Fan Z, Han Y, Bai X, Wang A, Zhang J, Wang J, Zhang K, et al: SIRT3 functions as an eraser of histone H3K9 lactylation to modulate transcription for inhibiting the progression of esophageal cancer. Mol Cell Proteomics. 24:1009732025. View Article : Google Scholar : PubMed/NCBI

124 

Zhai G, Niu Z, Jiang Z, Zhao F, Wang S, Chen C, Zheng W, Wang A, Zang Y, Han Y and Zhang K: DPF2 reads histone lactylation to drive transcription and tumorigenesis. Proc Natl Acad Sci USA. 121:e24214961212024. View Article : Google Scholar : PubMed/NCBI

125 

Nunez R, Sidlowski PFW, Steen EA, Wynia-Smith SL, Sprague DJ, Keyes RF and Smith BC: The TRIM33 bromodomain recognizes histone lysine lactylation. ACS Chem Biol. 19:2418–2428. 2024. View Article : Google Scholar : PubMed/NCBI

126 

Pan RY, He L, Zhang J, Liu X, Liao Y, Gao J, Liao Y, Yan Y, Li Q, Zhou X, et al: Positive feedback regulation of microglial glucose metabolism by histone H4 lysine 12 lactylation in Alzheimer's disease. Cell Metab. 34:634–648.e6. 2022. View Article : Google Scholar : PubMed/NCBI

127 

Susser LI, Nguyen MA, Geoffrion M, Emerton C, Ouimet M, Khacho M and Rayner KJ: Mitochondrial fragmentation promotes inflammation resolution responses in macrophages via histone lactylation. Mol Cell Biol. 43:531–546. 2023. View Article : Google Scholar : PubMed/NCBI

128 

Chen J, Zhang M, Liu Y, Zhao S, Wang Y, Wang M, Niu W, Jin F and Li Z: Histone lactylation driven by mROS-mediated glycolytic shift promotes hypoxic pulmonary hypertension. J Mol Cell Biol. 14:mjac0732023. View Article : Google Scholar : PubMed/NCBI

129 

An Z, Hu H, Wang Q, Qiu Y, Chu J, Xia Y and Li S: Dietary Selenium deficiency activates the NLRP3 inflammasome to induce gallbladder pyroptosis by regulating glycolysis and histone lactylation through ROS/HIF-1α pathway. J Nutr Biochem. 147:1101182025. View Article : Google Scholar : PubMed/NCBI

130 

Lv M, Zhou W, Hao Y, Li F, Zhang H, Yao X, Shi Y and Zhang L: Structural insights into the specific recognition of mitochondrial ribosome-binding factor hsRBFA and 12 S rRNA by methyltransferase METTL15. Cell Discov. 10:112024. View Article : Google Scholar : PubMed/NCBI

131 

Li X, Chen M, Chen X, He X, Li X, Wei H, Tan Y, Min J, Azam T, Xue M, et al: TRAP1 drives smooth muscle cell senescence and promotes atherosclerosis via HDAC3-primed histone H4 lysine 12 lactylation. Eur Heart J. 45:4219–4235. 2024. View Article : Google Scholar : PubMed/NCBI

132 

Yang L, Zuo S, Jia R, Gu X, Liao Q, Hua Y, Ge S, He M, Fan J, Tong X, et al: Lactylation-boosted polycomb repression of KLF4 elicits glycolysis in retinoblastoma: A positive feedback circuit between histone modifications. Cancer Lett. 625:2178042025. View Article : Google Scholar : PubMed/NCBI

133 

Gaffney DO, Jennings EQ, Anderson CC, Marentette JO, Shi T, Schou Oxvig AM, Streeter MD, Johannsen M, Spiegel DA, Chapman E, et al: Non-enzymatic lysine lactoylation of glycolytic enzymes. Cell Chem Biol. 27:206–213.e6. 2020. View Article : Google Scholar : PubMed/NCBI

134 

Tan Q, Liu M and Tao X: Targeting lactylation: From metabolic reprogramming to precision therapeutics in liver diseases. Biomolecules. 15:11782025. View Article : Google Scholar : PubMed/NCBI

135 

Varner EL, Trefely S, Bartee D, von Krusenstiern E, Izzo L, Bekeova C, O'Connor RS, Seifert EL, Wellen KE, Meier JL and Snyder NW: Quantification of lactoyl-CoA (lactyl-CoA) by liquid chromatography mass spectrometry in mammalian cells and tissues. Open Biol. 10:2001872020. View Article : Google Scholar : PubMed/NCBI

136 

Zhang D, Gao J, Zhu Z, Mao Q, Xu Z, Singh PK, Rimayi CC, Moreno-Yruela C, Xu S, Li G, et al: Lysine L-lactylation is the dominant lactylation isomer induced by glycolysis. Nat Chem Biol. 21:91–99. 2025. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Jia Z, Lu S, Wang Z and Ge P: From mechanism to targeted therapy: Advances in histone lactylation‑driven cancer progression (Review). Oncol Lett 31: 28, 2026.
APA
Jia, Z., Lu, S., Wang, Z., & Ge, P. (2026). From mechanism to targeted therapy: Advances in histone lactylation‑driven cancer progression (Review). Oncology Letters, 31, 28. https://doi.org/10.3892/ol.2025.15381
MLA
Jia, Z., Lu, S., Wang, Z., Ge, P."From mechanism to targeted therapy: Advances in histone lactylation‑driven cancer progression (Review)". Oncology Letters 31.1 (2026): 28.
Chicago
Jia, Z., Lu, S., Wang, Z., Ge, P."From mechanism to targeted therapy: Advances in histone lactylation‑driven cancer progression (Review)". Oncology Letters 31, no. 1 (2026): 28. https://doi.org/10.3892/ol.2025.15381
Copy and paste a formatted citation
x
Spandidos Publications style
Jia Z, Lu S, Wang Z and Ge P: From mechanism to targeted therapy: Advances in histone lactylation‑driven cancer progression (Review). Oncol Lett 31: 28, 2026.
APA
Jia, Z., Lu, S., Wang, Z., & Ge, P. (2026). From mechanism to targeted therapy: Advances in histone lactylation‑driven cancer progression (Review). Oncology Letters, 31, 28. https://doi.org/10.3892/ol.2025.15381
MLA
Jia, Z., Lu, S., Wang, Z., Ge, P."From mechanism to targeted therapy: Advances in histone lactylation‑driven cancer progression (Review)". Oncology Letters 31.1 (2026): 28.
Chicago
Jia, Z., Lu, S., Wang, Z., Ge, P."From mechanism to targeted therapy: Advances in histone lactylation‑driven cancer progression (Review)". Oncology Letters 31, no. 1 (2026): 28. https://doi.org/10.3892/ol.2025.15381
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team