ArticleCancer chemotherapy and pharmacology2017
Synthetic lethality in malignant pleural mesothelioma with PARP1 inhibition.
Article in Cancer chemotherapy and pharmacology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
42 citing papers in PubMed, 62 citations in OpenAlex.
- Phase II Trial of the PARP Inhibitor, Niraparib, in BAP1 and Other DNA Damage Response Pathway-Deficient Neoplasms.JCO precision oncology · 2024Trial
- Molecular profiling and personalized medicine within EURACAN in the SPECTA Arcagen study in comparison to the France Genomic Medicine 2025 Plan in the AURAGEN platform in peritoneal mesotheliomas.Translational oncology · 2026Article
- Spatial immune profiling complements genomic sequencing in biliary tract cancer: hypothesis-generating use cases.ESMO gastrointestinal oncology · 2026Article
- Review
- Molecular Insights into Pleural Mesothelioma: Unveiling Pathogenic Mechanisms and Therapeutic Opportunities.Diagnostics (Basel, Switzerland) · 2025Review
- Genomic characterization and detection of potential therapeutic targets for peritoneal mesothelioma in current practice.Clinical and experimental medicine · 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
- Complete clinical remission of malignant peritoneal mesothelioma with systemic pemetrexed and bevacizumab in a patient with a BAP1 mutation.BMJ case reports · 2023Article
- Review
- Clinical Next Generation Sequencing Application in Mesothelioma: Finding a Golden Needle in the Haystack.Cancers · 2023Review
- Target Therapy in Malignant Pleural Mesothelioma: Hope or Mirage?International journal of molecular sciences · 2023Review
- BAP1 as a guardian of genome stability: implications in human cancer.Experimental & molecular medicine · 2023Review
- Current Evidence and Future Perspectives about the Role of PARP Inhibitors in the Treatment of Thoracic Cancers.OncoTargets and therapy · 2023Review
- The Rocky Road from Preclinical Findings to Successful Targeted Therapy in Pleural Mesothelioma.International journal of molecular sciences · 2022Review
- Molecular Alterations in Malignant Pleural Mesothelioma: A Hope for Effective Treatment by Targeting YAP.Targeted oncology · 2022Review
- DNA repair and damage pathways in mesothelioma development and therapy.Cancer cell international · 2022Review
- Clinical Benefit of Niraparib to TKI/mTORi-Resistance Metastatic ccRCC WithFrontiers in oncology · 2022Article
- Natural phytochemicals prevent side effects inFrontiers in pharmacology · 2022Review
- Phase 2 Study of Olaparib in Malignant Mesothelioma and Correlation of Efficacy With Germline or Somatic Mutations inJTO clinical and research reports · 2021Article
- Integrated genomics point to immune vulnerabilities in pleural mesothelioma.Scientific reports · 2021Observational
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Malignant pleural mesotheliomas (MPM) are most often surgically unresectable, and they respond poorly to current chemotherapy and radiation therapy. Between 23 and 64% of malignant pleural mesothelioma have somatic inactivating mutations in the BAP1 gene. BAP1 is a homologous recombination (HR) DNA repair component found in the BRCA1/BARD1 complex. Similar to BRCA1/2 deficient cancers, mutation in the BAP1 gene leads to a deficient HR pathway and increases the reliance on other DNA repair pathways. We hypothesized that BAP1-mutant MPM would require PARP1 for survival, similar to the BRCA1/2 mutant breast and ovarian cancers. Therefore, we used the clinical PARP1 inhibitors niraparib and olaparib to assess whether they could induce synthetic lethality in MPM. Surprisingly, we found that all MPM cell lines examined, regardless of BAP1 status, were addicted to PARP1-mediated DNA repair for survival. We found that niraparib and olaparib exposure markedly decreased clonal survival in multiple MPM cell lines, with and without BAP1 mutations. This clonal cell death may be due to the extensive replication fork collapse and genomic instability that PARP1 inhibition induces in MPM cells. The requirement of MPM cells for PARP1 suggests that they may generally arise from defects in HR DNA repair. More importantly, these data demonstrate that the PARP1 inhibitors could be effective in the treatment of MPM, for which little effective therapy exists.
Indexed as
Identifiers
What OpenQuestion holds
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.