ArticleBritish journal of cancer2021
Essential role of the histone lysine demethylase KDM4A in the biology of malignant pleural mesothelioma (MPM).
Article in British journal of cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 12 citations in OpenAlex.
- A novel combination approach targeting P300 and DNA-PK exploits epigenetic dependencies in acute myeloid leukemia.Molecular therapy. Oncology · 2026Article
- Multi-omics integration in malignant pleural mesothelioma: from molecular evolution and immune ecosystems to precision therapy.Frontiers in oncology · 2026Review
- Sema7a drives an immunosuppressive microenvironment of breast cancer via Kdm4a-mediated DNA replication regulation.Communications biology · 2025Article
- Review
- Malignant Pleural Mesothelioma: From Pathophysiology to Innovative Actionable Targets.Cancers · 2025Review
- Origins of Catalysis in Non-Heme Fe(II)/2-Oxoglutarate-Dependent Histone Lysine Demethylase KDM4A with Differently Methylated Histone H3 Peptides.Chemistry (Weinheim an der Bergstrasse, Germany) · 2025Article
- [Advances in Targeted Therapy for Malignant Pleural Mesothelioma].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2024Review
- Multiple Comprehensive Analyses Identify Lysine Demethylase KDM as a Potential Therapeutic Target for Pancreatic Cancer.International journal of medical sciences · 2024Article
- Role of primary aging hallmarks in Alzheimer´s disease.Theranostics · 2023Review
- Recent Advances with KDM4 Inhibitors and Potential Applications.Journal of medicinal chemistry · 2022Review
- Novel Therapeutic Targets and Immune Dysfunction in Malignant Pleural Mesothelioma.Frontiers in pharmacology · 2021Review
Corrections and comments
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Authors and funding
21 authors at 9 institutions in 2 countries.
Funding
Abstract
backgroundMalignant pleural mesothelioma (MPM) is a highly aggressive cancer with a dismal prognosis. There is increasing interest in targeting chromatin regulatory pathways in difficult-to-treat cancers. In preliminary studies, we found that KDM4A (lysine-specific histone demethylase 4) was overexpressed in MPM.
methodsKDM4A protein expression was determined by immunohistochemistry or immunoblotting. Functional inhibition of KDM4A by targeted knockdown and small molecule drugs was correlated to cell growth using cell lines and a xenograft mouse model. Gene expression profiling was performed to identify KDM4A-dependent signature pathways.
resultsLevels of KDM4A were found to be significantly elevated in MPM patients compared to normal mesothelial tissue. Inhibiting the enzyme activity efficiently reduced cell growth in vitro and reduced tumour growth in vivo. KDM4A inhibitor-induced apoptosis was further enhanced by the BH3 mimetic navitoclax. KDM4A expression was associated with pathways involved in cell growth and DNA repair. Interestingly, inhibitors of the DNA damage and replication checkpoint regulators CHK1 (prexasertib) and WEE1 (adavosertib) within the DNA double-strand break repair pathway, cooperated in the inhibition of cell growth.
conclusionsThe results establish a novel and essential role for KDM4A in growth in preclinical models of MPM and identify potential therapeutic approaches to target KDM4A-dependent vulnerabilities.
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