ArticleNature communications2020
Proteasome inhibitor-induced modulation reveals the spliceosome as a specific therapeutic vulnerability in multiple myeloma.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
- Alternative splicing and cancer: a systematic review.Signal transduction and targeted therapy · 2021Pooled it
- Dynamic multimodal survival prediction in multiple myeloma integrating gene expression, longitudinal laboratory measurements, and treatment history.Briefings in bioinformatics · 2026Article
- Dysregulation of SRSF11 in Cancer: Mechanistic Insights and Biomarker Potential for Diagnosis and Therapy.Journal of Cancer · 2026Review
- Unlocking the undruggable spliceosome: generative AI and structural dynamics in cancer therapy.Frontiers in cell and developmental biology · 2026Review
- Targeting the RBM39-MEK5 axis synergizes with bortezomib to inhibit the malignant growth of multiple myeloma.Blood advances · 2025Article
- Targeting CLK2 and serine/arginine-rich splicing factors inhibits multiple myeloma through downregulating RAE1 by nonsense-mediated mRNA decay mechanism.Cancer science · 2025Article
- Characterization of driver mutations identifies gene signatures predictive of prognosis and treatment sensitivity in multiple myeloma.The oncologist · 2024Article
- Integrative chemoproteomics reveals anticancer mechanisms of silver(i) targeting the proteasome regulatory complex.Chemical science · 2024Article
- Nicotinamide Mononucleotide (NMN) Works in Type 2 Diabetes through Unexpected Effects in Adipose Tissue, Not by Mitochondrial Biogenesis.International journal of molecular sciences · 2024Article
- A neutrophil extracellular trap-related risk score predicts prognosis and characterizes the tumor microenvironment in multiple myeloma.Scientific reports · 2024Article
- PRRGO: A Tool for Visualizing and Mapping Globally Expressed Genes in Public Gene Expression Omnibus RNA-Sequencing Studies to PageRank-scored Gene Ontology Terms.bioRxiv : the preprint server for biology · 2024Article
- Broad variation in response of individual introns to splicing inhibitors in a humanized yeast strain.RNA (New York, N.Y.) · 2024Article
- Neoantigens in cancer immunotherapy: focusing on alternative splicing.Frontiers in immunology · 2024Review
- Broad variation in response of individual introns to splicing inhibitors in a humanized yeast strain.bioRxiv : the preprint server for biology · 2023Article
- Transcriptional repression upon S phase entry protects genome integrity in pluripotent cells.Nature structural & molecular biology · 2023Article
- Ancistrocladinium A Induces Apoptosis in Proteasome Inhibitor-Resistant Multiple Myeloma Cells: A Promising Therapeutic Agent Candidate.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Ex vivo drug response heterogeneity reveals personalized therapeutic strategies for patients with multiple myeloma.Nature cancer · 2023Article
- Chronic Exposure to Low Levels of Parabens Increases Mammary Cancer Growth and Metastasis in Mice.Endocrinology · 2023Article
- Proteomic characterization of post-translational modifications in drug discovery.Acta pharmacologica Sinica · 2022Review
- Article
Corrections and comments
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Authors and funding
19 authors at 2 institutions in 1 country.
Funding
Abstract
Enhancing the efficacy of proteasome inhibitors (PI) is a central goal in myeloma therapy. We proposed that signaling-level responses after PI may reveal new mechanisms of action that can be therapeutically exploited. Unbiased phosphoproteomics after treatment with the PI carfilzomib surprisingly demonstrates the most prominent phosphorylation changes on splicing related proteins. Spliceosome modulation is invisible to RNA or protein abundance alone. Transcriptome analysis after PI demonstrates broad-scale intron retention, suggestive of spliceosome interference, as well as specific alternative splicing of protein homeostasis machinery components. These findings lead us to evaluate direct spliceosome inhibition in myeloma, which synergizes with carfilzomib and shows potent anti-tumor activity. Functional genomics and exome sequencing further support the spliceosome as a specific vulnerability in myeloma. Our results propose splicing interference as an unrecognized modality of PI mechanism, reveal additional modes of spliceosome modulation, and suggest spliceosome targeting as a promising therapeutic strategy in myeloma.
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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.