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Targeting lactylation in hepatocellular carcinoma: Mechanistic insights and therapeutic opportunities (Review)

  • Authors:
    • Lianting Chen
    • Feiqiong Gao
    • Qianru Mei
    • Yujie Li
    • Qun Cai
    • Xudong Feng
  • View Affiliations / Copyright

    Affiliations: Department of Clinical Laboratory, Ningbo Medical Center Lihuili Hospital, The Affiliated Lihuili Hospital of Ningbo University, Ningbo, Zhejiang 315000, P.R. China, Department of Endocrinology, Affiliated Hangzhou First People's Hospital, School of Medicine, Westlake University, Hangzhou, Zhejiang 310006, P.R. China, Department of Infectious Diseases and Liver Diseases, Ningbo Medical Center Lihuili Hospital, The Affiliated Lihuili Hospital of Ningbo University, Ningbo, Zhejiang 315000, P.R. China
    Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 204
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    Published online on: May 28, 2026
       https://doi.org/10.3892/ijmm.2026.5875
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Abstract

Hepatocellular carcinoma (HCC) is a malignant tumor characterized by profound metabolic reprogramming and a pronounced Warburg effect, resulting in excessive lactate accumulation in the tumor microenvironment (TME). Traditionally regarded as a metabolic byproduct, lactate has recently been recognized as a substrate for lactylation, offering new insights into tumorigenesis and cancer progression. The present review systematically summarized the molecular basis of lactylation and delineated its regulatory network in HCC. It focused on how lactylation contributes to the malignant phenotype of HCC cells and reshapes the TME, highlighting its roles in tumor progression and metabolic‑immune interactions. Based on current evidence, lactylation‑related features show potential translational value in the diagnosis, treatment and prognosis of HCC. A deeper understanding of lactylation mechanisms may provide novel insights and strategies for precision therapy in HCC.
View Figures

Figure 1

Molecular regulatory network of
lactylation. HDAC, histone deacetylase; TCA, tricarboxylic acid;
LDH, lactate dehydrogenase.

Figure 2

Impact of lactylation on the
pathogenesis and progression of hepatocellular carcinoma.

Figure 3

Lactylation promotes tumor
progression by regulating the TME. TME, tumor microenvironment;
TAM, tumor-associated macrophage; CTL, cytotoxic T lymphocyte; DC,
dendritic cell; NK cell, natural killer cell; NDRG3, N-Myc
downstream regulatory gene 3; HIF, hypoxia-inducible factor; TCA,
tricarboxylic acid; LDH, lactate dehydrogenase.

Figure 4

Therapeutic targeting of the
lactate-lactylation axis in hepatocellular carcinoma. LDH, lactate
dehydrogenase; HDAC, histone deacetylase; MCT, monocarboxylate
transporter.
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Copy and paste a formatted citation
Spandidos Publications style
Chen L, Gao F, Mei Q, Li Y, Cai Q and Feng X: Targeting lactylation in hepatocellular carcinoma: Mechanistic insights and therapeutic opportunities (Review). Int J Mol Med 58: 204, 2026.
APA
Chen, L., Gao, F., Mei, Q., Li, Y., Cai, Q., & Feng, X. (2026). Targeting lactylation in hepatocellular carcinoma: Mechanistic insights and therapeutic opportunities (Review). International Journal of Molecular Medicine, 58, 204. https://doi.org/10.3892/ijmm.2026.5875
MLA
Chen, L., Gao, F., Mei, Q., Li, Y., Cai, Q., Feng, X."Targeting lactylation in hepatocellular carcinoma: Mechanistic insights and therapeutic opportunities (Review)". International Journal of Molecular Medicine 58.2 (2026): 204.
Chicago
Chen, L., Gao, F., Mei, Q., Li, Y., Cai, Q., Feng, X."Targeting lactylation in hepatocellular carcinoma: Mechanistic insights and therapeutic opportunities (Review)". International Journal of Molecular Medicine 58, no. 2 (2026): 204. https://doi.org/10.3892/ijmm.2026.5875
Copy and paste a formatted citation
x
Spandidos Publications style
Chen L, Gao F, Mei Q, Li Y, Cai Q and Feng X: Targeting lactylation in hepatocellular carcinoma: Mechanistic insights and therapeutic opportunities (Review). Int J Mol Med 58: 204, 2026.
APA
Chen, L., Gao, F., Mei, Q., Li, Y., Cai, Q., & Feng, X. (2026). Targeting lactylation in hepatocellular carcinoma: Mechanistic insights and therapeutic opportunities (Review). International Journal of Molecular Medicine, 58, 204. https://doi.org/10.3892/ijmm.2026.5875
MLA
Chen, L., Gao, F., Mei, Q., Li, Y., Cai, Q., Feng, X."Targeting lactylation in hepatocellular carcinoma: Mechanistic insights and therapeutic opportunities (Review)". International Journal of Molecular Medicine 58.2 (2026): 204.
Chicago
Chen, L., Gao, F., Mei, Q., Li, Y., Cai, Q., Feng, X."Targeting lactylation in hepatocellular carcinoma: Mechanistic insights and therapeutic opportunities (Review)". International Journal of Molecular Medicine 58, no. 2 (2026): 204. https://doi.org/10.3892/ijmm.2026.5875
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