ArticleScience advances2021
Targeting the spliceosome through RBM39 degradation results in exceptional responses in high-risk neuroblastoma models.
Article in Science advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
What it found
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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.
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Who cites it
48 citing papers in PubMed, 102 citations in OpenAlex.
- Targeting PRMT5 Inhibitor-Induced Adaptation in Pancreatic Cancer with the RBM39 Degrader Indisulam.Cancer research communications · 2026Article
- DRIVE: a comprehensive resource deciphering drug-induced transcriptomic and splicing response in cancer cell.Neoplasia (New York, N.Y.) · 2026Article
- MBNL1 hijacks a structured single-stranded distal DNA element to sustainScience advances · 2026Article
- Targeting "undruggable" cancer proteins: pharmacological challenges and emerging strategies.Translational cancer research · 2026Review
- Article
- GSPT1-specific protein degradation is effective in preclinical models of chemoresistant MYCN-amplified neuroblastoma.Journal of experimental & clinical cancer research : CR · 2026Article
- RNA-binding motif proteins as context-dependent regulators of tumor-immune crosstalk, genome stability, and therapeutic vulnerabilities in cancer.Frontiers in immunology · 2026Review
- RNA Splicing as a Therapeutic Target in Cancer.Annual review of pharmacology and toxicology · 2026Review
- Targeting TRIM59 impairs RNA splicing and promotes neuroblastoma differentiation and therapeutic responses.Journal of experimental & clinical cancer research : CR · 2025Article
- Transcriptomic and epigenetic profiling of neuroblastoma states in response to RBM39 degrader.Scientific data · 2025Article
- A Yeast-Based High-Throughput Screening Platform for the Discovery of Novel pre-mRNA Splicing Modulators.bioRxiv : the preprint server for biology · 2025Article
- RBM39 Promotes Base Excision Repair to Facilitate the Progression of HCC by Stabilising OGG1 mRNA.Cell proliferation · 2025Article
- RBM39 degrader invigorates innate immunity to eradicate neuroblastoma despite cancer cell plasticity.Nature communications · 2025Article
- Targeting the RBM39-MEK5 axis synergizes with bortezomib to inhibit the malignant growth of multiple myeloma.Blood advances · 2025Article
- The RBM39 degrader indisulam inhibits acute megakaryoblastic leukemia by altering the alternative splicing of ZMYND8.Cell & bioscience · 2025Article
- RNA-binding motif protein RBM39 enhances the proliferation of gastric cancer cells by facilitating an oncogenic splicing switch in MRPL33.Acta pharmacologica Sinica · 2025Article
- Article
- Review
- Molecular regulation and therapeutic targeting ofFrontiers in cell and developmental biology · 2025Review
- Article
Corrections and comments
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Authors and funding
22 authors at 5 institutions in 2 countries.
Funding
Abstract
Aberrant alternative pre-mRNA splicing plays a critical role in MYC-driven cancers and therefore may represent a therapeutic vulnerability. Here, we show that neuroblastoma, a MYC-driven cancer characterized by splicing dysregulation and spliceosomal dependency, requires the splicing factor RBM39 for survival. Indisulam, a “molecular glue” that selectively recruits RBM39 to the CRL4-DCAF15 E3 ubiquitin ligase for proteasomal degradation, is highly efficacious against neuroblastoma, leading to significant responses in multiple high-risk disease models, without overt toxicity. Genetic depletion or indisulam-mediated degradation of RBM39 induces significant genome-wide splicing anomalies and cell death. Mechanistically, the dependency on RBM39 and high-level expression of DCAF15 determine the exquisite sensitivity of neuroblastoma to indisulam. Our data indicate that targeting the dysregulated spliceosome by precisely inhibiting RBM39, a vulnerability in neuroblastoma, is a valid therapeutic strategy.
Identifiers
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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.