ArticleCell reports. Medicine2023
Genetic screens reveal new targetable vulnerabilities in BAP1-deficient mesothelioma.
Article in Cell reports. Medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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The trial behind it
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Who cites it
15 citing papers in PubMed, 17 citations in OpenAlex.
- PRC2 loss impairs small cell lung cancer tumorigenesis and enhances sensitivity to G9a/GLP inhibition.Communications biology · 2026Article
- Review
- Multi-omics integration in malignant pleural mesothelioma: from molecular evolution and immune ecosystems to precision therapy.Frontiers in oncology · 2026Review
- Cholesterol biosynthesis as a drug-induced vulnerability in diffuse large B cell lymphoma insensitive to EZH2 inhibition.Neoplasia (New York, N.Y.) · 2025Article
- Prospective Analysis of Mesotheliomas in Subjects With BAP1 Cancer Syndrome: Clinical Characteristics and Epigenetic Correlates of Disease.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2025Observational
- De novo pyrimidine synthesis is a collateral metabolic vulnerability in NF2-deficient mesothelioma.EMBO molecular medicine · 2025Article
- 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
- Cholangiocarcinoma Targeted Therapies: Mechanisms of Action and Resistance.The American journal of pathology · 2025Review
- Leukocyte immunoglobulin-like receptor B1 (LILRB1) protects human multiple myeloma cells from ferroptosis by maintaining cholesterol homeostasis.Nature communications · 2024Article
- Saturation genome editing of BAP1 functionally classifies somatic and germline variants.Nature genetics · 2024Article
- Combination of EZH2 and ATM inhibition in BAP1-deficient mesothelioma.British journal of cancer · 2024Article
- The genetic susceptibility in the development of malignant pleural mesothelioma: somatic and germline variants, clinicopathological features and implication in practical medical/surgical care: a narrative review.Journal of thoracic disease · 2024Review
- Combined Inhibition of EZH2 and FGFR is Synergistic in BAP1-deficient Malignant Mesothelioma.Cancer research communications · 2024Article
- Clinical Next Generation Sequencing Application in Mesothelioma: Finding a Golden Needle in the Haystack.Cancers · 2023Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
More than half of patients with malignant mesothelioma show alterations in the BAP1 tumor-suppressor gene. Being a member of the Polycomb repressive deubiquitinating (PR-DUB) complex, BAP1 loss results in an altered epigenome, which may create new vulnerabilities that remain largely unknown. Here, we performed a CRISPR-Cas9 kinome screen in mesothelioma cells that identified two kinases in the mevalonate/cholesterol biosynthesis pathway. Furthermore, our analysis of chromatin, expression, and genetic perturbation data in mesothelioma cells suggests a dependency on PR complex 2 (PRC2)-mediated silencing. Pharmacological inhibition of PRC2 elevates the expression of cholesterol biosynthesis genes only in BAP1-deficient mesothelioma, thereby sensitizing these cells to the combined targeting of PRC2 and the mevalonate pathway. Finally, by subjecting autochthonous Bap1-deficient mesothelioma mice or xenografts to mevalonate pathway inhibition (zoledronic acid) and PRC2 inhibition (tazemetostat), we demonstrate a potent anti-tumor effect, suggesting a targeted combination therapy for Bap1-deficient mesothelioma.
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Registered trials
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.