ArticleBritish journal of cancer2024
Combination of EZH2 and ATM inhibition in BAP1-deficient mesothelioma.
Article in British journal of cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 9 citations in OpenAlex.
- BAP1 Loss Might Be a Predictive Biomarker for Immunotherapy Response in Pleural Mesothelioma.Thoracic cancer · 2026Article
- The Role of EZH2 ın Malıgnant Pleural Mesothelıoma and Beyond: Current Practıce and Future Perspectıves.Current oncology reports · 2026Review
- Review
- Article
- Review
- From biology to therapy: current standards and emerging strategies in pleural mesothelioma.Frontiers in oncology · 2026Review
- [Recent Advances in Medical Treatment of Malignant Pleural Mesothelioma].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2025Review
- BAP1 Mutations and Pleural Mesothelioma: Genetic Insights, Clinical Implications, and Therapeutic Perspectives.Cancers · 2025Review
- An overview of BAP1 biological functions and current therapeutics.Biochimica et biophysica acta. Reviews on cancer · 2025Review
- ERS Congress 2024: highlights from the Thoracic Oncology Assembly.ERJ open research · 2025Article
- Getting the right combination to break the epigenetic code.Nature reviews. Clinical oncology · 2025Review
- Targeted Therapy in Mesotheliomas: Uphill All the Way.Cancers · 2024Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
Abstract
backgroundMore than half of mesothelioma tumours show alterations in the tumour suppressor gene BAP1. BAP1-deficient mesothelioma is shown to be sensitive to EZH2 inhibition in preclinical settings but only showed modest efficacy in clinical trial. Adding a second inhibitor could potentially elevate EZH2i treatment efficacy while preventing acquired resistance at the same time.
methodsA focused drug synergy screen consisting of 20 drugs was performed by combining EZH2 inhibition with a panel of anti-cancer compounds in mesothelioma cell lines. The compounds used are under preclinical investigation or already used in the clinic. The synergistic potential of the combinations was assessed by using the Bliss model. To validate our findings, in vivo xenograft experiments were performed.
resultsCombining EZH2i with ATMi was found to have synergistic potential against BAP1-deficient mesothelioma in our drug screen, which was validated in clonogenicity assays. Tumour growth inhibition potential was significantly increased in BAP1-deficient xenografts. In addition, we observe lower ATM levels upon depletion of BAP1 and hypothesise that this might be mediated by E2F1.
conclusionsWe demonstrated the efficacy of the combination of ATM and EZH2 inhibition against BAP1-deficient mesothelioma in preclinical models, indicating the potential of this combination as a novel treatment modality using BAP1 as a biomarker.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.