ArticleJournal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer2020
Sensitivity of Mesothelioma Cells to PARP Inhibitors Is Not Dependent on BAP1 but Is Enhanced by Temozolomide in Cells With High-Schlafen 11 and Low-O6-methylguanine-DNA Methyltransferase Expression.
Article in Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 67 citations in OpenAlex.
- Patient-Derived Organoid Models and Precision HIPEC in Diffuse Malignant Peritoneal Mesothelioma: Modeling Heterogeneity to Address Recurrence.International journal of molecular sciences · 2026Review
- Schlafen 11 Is Overexpressed in Multiple Myeloma and Undergoes Nucleolar Translocation in Response to Bortezomib.Cancer research communications · 2026Article
- BAP1 and USP1 cooperate to regulate FANCD2 stability and cell proliferation in mesothelioma cells.Cell death & disease · 2026Article
- Schlafen 11 (SLFN11) overexpression and nucleolar localization in response to bortezomib in multiple myeloma.bioRxiv : the preprint server for biology · 2026Article
- Review
- PARP inhibitors across different malignancies: clinical applications, resistance mechanisms, and strategies to enhance efficacy through combination therapies.Frontiers in cell and developmental biology · 2026Review
- Enhanced tumor suppression in patient-derived temozolomide-resistant glioblastoma cells using a combination treatment of Olaparib and FK866.BMC cancer · 2025Article
- Molecular Insights into Pleural Mesothelioma: Unveiling Pathogenic Mechanisms and Therapeutic Opportunities.Diagnostics (Basel, Switzerland) · 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
- Redox regulation: mechanisms, biology and therapeutic targets in diseases.Signal transduction and targeted therapy · 2025Review
- Phosphorylation-mediated conformational change regulates human SLFN11.Nature communications · 2024Article
- SLFN12 Expression Significantly Effects the Response to Chemotherapy Drugs in Triple-Negative Breast Cancer.Cancers · 2024Article
- Review
- Article
- Targeted Approaches to Treatment of Pleural Mesothelioma: A Review.JCO precision oncology · 2023Review
- Chinese expert consensus on the diagnosis and treatment of malignant pleural mesothelioma.Thoracic cancer · 2023Article
- BAP1 Loss Is Associated with Higher ASS1 Expression in Epithelioid Mesothelioma: Implications for Therapeutic Stratification.Molecular cancer research : MCR · 2023Article
- BAP1 as a guardian of genome stability: implications in human cancer.Experimental & molecular medicine · 2023Review
- MEK1 drives oncogenic signaling and interacts with PARP1 for genomic and metabolic homeostasis in malignant pleural mesothelioma.Cell death discovery · 2023Article
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18 authors at 3 institutions in 1 country.
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Abstract
introductionBRCA1-associated protein-1 (BAP1), a nuclear deubiquitinase thought to be involved in DNA double-strand break repair, is frequently mutated in mesothelioma. Because poly(adenosine diphosphate-ribose) polymerase inhibitors (PARPIs) induce synthetic lethality in BRCA1/2 mutant cancers, we evaluated whether BAP1 inactivating mutations confer sensitivity to PARPIs in mesothelioma and if combination therapy with temozolomide (TMZ) would be beneficial.
methodsA total of 10 patient-derived mesothelioma cell lines were generated and characterized for BAP1 mutation status, protein expression, nuclear localization, and sensitivity to the PARPIs, olaparib, and talazoparib, alone or in combination with TMZ. BAP1 deubiquitinase (DUB) activity was evaluated by ubiquitin with 7-amido-4-methylcoumarin assay. BAP1 knockout mesothelioma cell lines were generated by CRISPR-Cas9. Because Schlafen 11 (SLFN11) and O
resultsBAP1 mutations or copy-number alterations, or both were present in all 10 cell lines. Nonetheless, four cell lines exhibited intact DUB activity and two had nuclear BAP1 localization. Half maximal-inhibitory concentrations of olaparib and talazoparib ranged from 4.8 μM to greater than 50 μM and 0.039 μM to greater than 5 μM, respectively, classifying them into sensitive (two) or resistant (seven) cells, independent of their BAP1 status. Cell lines with BAP1 knockout resulted in the loss of BAP1 DUB activity but did not increase sensitivity to talazoparib. Response to PARPI tended to be associated with high SLFN11 expression, and combination with temozolomide increased sensitivity of cells with low or no MGMT expression.
conclusionsBAP1 status does not determine sensitivity to PARPIs in patient-derived mesothelioma cell lines. Combination of PARPI with TMZ may be beneficial for patients whose tumors have high SLFN11 and low or no MGMT expression.
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