ArticleEBioMedicine2019
Splicing modulation as novel therapeutic strategy against diffuse malignant peritoneal mesothelioma.
Article in EBioMedicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
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, 1 synthesis or guideline pooled it.
- Novel and Future Treatment Options in Mesothelioma: A Systematic Review.International journal of molecular sciences · 2022Pooled it
- Deconvoluting the multi-faceted roles of alternative splicing events in cancer: From underlying mechanisms to innovative therapeutics.Acta pharmaceutica Sinica. B · 2026Review
- The emerging roles of alternative splicing in modulating tumor immune responses and immunotherapies.Cell death and differentiation · 2026Review
- Dynamic evaluation of the glycolytic determinants LDH-A and GLUT-1 enhances prognostic significance and their inhibition affects the growth of mesothelioma spheroids.Molecular metabolism · 2026Article
- Novel Pyrazolo [1,5-a]-1,3,5-Triazine Derivatives as CDK7 Inhibitors: Synthesis and Biological Insights in Pancreatic Ductal Adenocarcinoma Models.ChemMedChem · 2025Article
- A common structural mechanism for RNA recognition by the SF3B complex in mRNA splicing and export.Nucleic acids research · 2025Article
- Unraveling resistance mechanisms to the novel nucleoside analog RX-3117 in lung cancer: insights into DNA repair, cell cycle dysregulation and targeting PKMYT1 for improved therapy.Journal of experimental & clinical cancer research : CR · 2025Article
- Determination of trunk neural crest cell fate and susceptibility to splicing perturbation by the DLC1-SF3B1-PHF5A splicing complex.Nature communications · 2025Article
- Review
- Review
- Targeting RNA splicing modulation: new perspectives for anticancer strategy?Journal of experimental & clinical cancer research : CR · 2025Review
- Radical hemithorax radiotherapy induces an increase in circulating PD-1Frontiers in immunology · 2025Article
- The splicing factor SF3B1 confers ferroptosis resistance and promotes lung adenocarcinoma progression via upregulation of SLC7A11.Cancer gene therapy · 2024Article
- The Impact of Spliceosome Inhibition in SF3B1-Mutated Uveal Melanoma.Investigative ophthalmology & visual science · 2024Article
- RPL22 is a tumor suppressor in MSI-high cancers and a splicing regulator of MDM4.Cell reports · 2024Article
- Exploring Splicing Modulation as an Innovative Approach to Combat Pancreatic Cancer: SF3B1 Emerges as a Prognostic Indicator and Therapeutic Target.International journal of biological sciences · 2024Article
- RPL22 is a tumor suppressor in MSI-high cancers and a key splicing regulator of MDM4.bioRxiv : the preprint server for biology · 2023Article
- 1,3,4-Oxadiazole and 1,3,4-Thiadiazole Nortopsentin Derivatives against Pancreatic Ductal Adenocarcinoma: Synthesis, Cytotoxic Activity, and Inhibition of CDK1.Marine drugs · 2023Article
- CDK12/13 promote splicing of proximal introns by enhancing the interaction between RNA polymerase II and the splicing factor SF3B1.Nucleic acids research · 2023Article
- Splicing Modulation Results in Aberrant Isoforms and Protein Products of p53 Pathway Genes and the Sensitization of B Cells to Non-Genotoxic MDM2 Inhibition.International journal of molecular sciences · 2023Article
Corrections and comments
- Commented on by
Authors and funding
19 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionTherapeutic options for diffuse malignant peritoneal mesothelioma (DMPM) are limited to surgery and locoregional chemotherapy. Despite improvements in survival rates, patients eventually succumb to disease progression. We investigated splicing deregulation both as molecular prognostic factor and potential novel target in DMPM, while we tested modulators of SF3b complex for antitumor activity.
methodsTissue-microarrays of 64 DMPM specimens were subjected to immunohistochemical assessment of SF3B1 expression and correlation to clinical outcome. Two primary cell cultures were used for gene expression profiling and in vitro screening of SF3b modulators. Drug-induced splicing alterations affecting downstream cellular pathways were detected through RNA sequencing. Ultimately, we established bioluminescent orthotopic mouse models to test the efficacy of splicing modulation in vivo.
resultsSpliceosomal genes are differentially upregulated in DMPM cells compared to normal tissues and high expression of SF3B1 correlated with poor clinical outcome in univariate and multivariate analysis. SF3b modulators (Pladienolide-B, E7107, Meayamycin-B) showed potent cytotoxic activity in vitro with IC50 values in the low nanomolar range. Differential splicing analysis of Pladienolide-B-treated cells revealed abundant alterations of transcripts involved in cell cycle, apoptosis and other oncogenic pathways. This was validated by RT-PCR and functional assays. E7107 demonstrated remarkable in vivo antitumor efficacy, with significant improvement of survival rates compared to vehicle-treated controls.
conclusionsSF3B1 emerged as a novel potential prognostic factor in DMPM. Splicing modulators markedly impair cancer cell viability, resulting also in potent antitumor activity in vivo. Our data designate splicing as a promising therapeutic target in DMPM.
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.