ReviewCancer drug resistance (Alhambra, Calif.)2025
Lactylation: a novel driver of drug resistance in the tumor microenvironment.
Review in Cancer drug resistance (Alhambra, Calif.), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- Intensification versus combination: revisiting the past and envisioning the future of LDHA inhibitors.Cancer chemotherapy and pharmacology · 2026Review
- Endogenous metabolite signaling orchestrates tumor immune evasion.Cell insight · 2026Review
- Crosstalk between lactylation and other post-translational modifications in health and diseases.Molecular biomedicine · 2026Review
- KAT2A-IGF2BP1-CXCL2 axis in the high lactate tumor microenvironment facilitates resistance to anti-PD-1 therapy in lung adenocarcinoma by recruiting myeloid-derived suppressor cells.Cell death & disease · 2026Article
- Histone lactylation: a novel epigenetic bridge linking cellular metabolism to benign and malignant gynecological diseases.Clinical epigenetics · 2026Review
- Hypoxia and lactate metabolism-related gene COL5A3 promotes triple negative breast cancer progression via DDR1/FAK/PI3K/AKT pathway.Biology direct · 2026Article
- Metabolic Signaling Meets Epigenetic Regulation: How Protein Lactylation Remodels the Tumor Immune Microenvironment in Gastric Cancer.Current issues in molecular biology · 2026Review
- Lysine lactylation-mediated post-translational modification: Molecular mechanisms and therapeutic target exploration in tumour drug resistance.Clinical and translational medicine · 2026Review
- Epigenetic regulation and posttranslational modifications of FXR: underlying mechanisms and implications in digestive diseases.Acta pharmacologica Sinica · 2026Review
- Machine learning-based integration identifies lactylation biomarkers for prognosis prediction and tumor microenvironment modulation in bladder cancer.Translational andrology and urology · 2026Article
- Lactylation as a metabolic-epigenetic switch: Mechanisms and roles in cancer, sepsis, trauma, inflammation, and tissue repair.Biochemistry and biophysics reports · 2026Review
- Roles of lactate and lactylation in tumor immune suppression and drug resistance.Frontiers in immunology · 2026Review
- Transferrin receptor serves a role in promoting PANoptosis in thyroid cancer.Oncology letters · 2026Article
- The tumor microenvironment in leukemia: molecular pathways of immune evasion.Frontiers in immunology · 2026Review
- Lactylation in urological malignancies: emerging mechanisms and therapeutic direction.Frontiers in cell and developmental biology · 2026Review
- The glycolysis-lactylation axis: a metabolic-epigenetic driver of immunosuppression and therapy resistance in cancer.Frontiers in immunology · 2026Review
- An AI-driven multi-omics framework identifies lactylation-mediated therapeutic targets to overcome drug resistance in ovarian cancer.NPJ precision oncology · 2025Article
- Protein crotonylation in cancer: mechanisms, functions, and therapeutic potential.Cell biology and toxicology · 2025Review
- The role of lactylation in breast cancer development: mechanisms, clinical translation and new strategies for treatment.Frontiers in oncology · 2025Review
- Lactylation in digestive system tumors: from mechanisms to therapeutic target.Frontiers in oncology · 2025Review
Corrections and comments
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lactylation, a novel lactate-derived lysine post-translational modification (PTM), has emerged as a critical epigenetic regulator driving drug resistance within the tumor microenvironment (TME). This review systematically delineates the enzymatic underpinnings of lactylation, its induction via the glycolysis-lactate axis influenced by key TME features (hypoxia, inflammation), and its multifaceted roles in promoting resistance. Specifically, lactylation orchestrates transcriptional reprogramming of resistance-associated genes (e.g., oncogenes, immune checkpoints, epithelial-mesenchymal transition factors), enhances DNA damage repair capacity (e.g., via NBS1/MRE11 lactylation), activates pro-survival autophagy, and modulates immunosuppressive signaling pathways (e.g., PI3K/AKT, NF-κB, JAK/STAT). Furthermore, it facilitates critical resistance phenotypes including immune evasion, metastasis, and angiogenesis. The review summarizes emerging therapeutic strategies targeting lactylation, such as inhibition of lactate production (LDHA/LDHB), lactate transport (MCT1/4), lactyltransferases (e.g., p300), or downstream effectors, highlighting their potential to overcome multifactorial resistance. However, elucidating the context-dependent roles, crosstalk with other PTMs, and developing specific inhibitors remain crucial for translating these insights into effective clinical interventions against resistant tumors.
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