ArticleCommunications biology2024
Targeting TRIP13 in favorable histology Wilms tumor with nuclear export inhibitors synergizes with doxorubicin.
Article in Communications biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 7 citations in OpenAlex.
- SMARCB1 missense mutants disrupt SWI/SNF complex stability and remodeling activity.Nature communications · 2026Article
- Wilms Tumor with Inferior Vena Cava Thrombus: Comparative Analysis of Clinical Characteristics and Outcomes.Current oncology (Toronto, Ont.) · 2026Article
- Review
- KPT-330, A New Candidate Drug for Targeting NOTCH1 Overexpression in T-cell Acute Lymphoblastic Leukemia, An In Vitro and Silico Study.Cell biochemistry and biophysics · 2025Article
- PD-L1 Expression is Mediated by microRNA Processing, Wnt/β-Catenin Signaling, and Chemotherapy in Wilms Tumor.Pediatric blood & cancer · 2025Article
- Consistently processed RNA sequencing data from 50 sources enriched for pediatric data.Scientific data · 2025Article
- Exportin-mediated nucleocytoplasmic transport maintains Pch2 homeostasis during meiosis.PLoS genetics · 2023Article
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Authors and funding
38 authors at 4 institutions in 1 country.
Funding
Abstract
Wilms tumor (WT) is the most common renal malignancy of childhood. Despite improvements in the overall survival, relapse occurs in ~15% of patients with favorable histology WT (FHWT). Half of these patients will succumb to their disease. Identifying novel targeted therapies remains challenging in part due to the lack of faithful preclinical in vitro models. Here we establish twelve patient-derived WT cell lines and demonstrate that these models faithfully recapitulate WT biology using genomic and transcriptomic techniques. We then perform loss-of-function screens to identify the nuclear export gene, XPO1, as a vulnerability. We find that the FDA approved XPO1 inhibitor, KPT-330, suppresses TRIP13 expression, which is required for survival. We further identify synergy between KPT-330 and doxorubicin, a chemotherapy used in high-risk FHWT. Taken together, we identify XPO1 inhibition with KPT-330 as a potential therapeutic option to treat FHWTs and in combination with doxorubicin, leads to durable remissions in vivo.
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Registered trials
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