ArticleCell reports. Medicine2025
Metabolic profiling of patient-derived organoids reveals nucleotide synthesis as a metabolic vulnerability in malignant rhabdoid tumors.
Article in Cell reports. Medicine, 2025. 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.
- Therapy-resistant lymphomas may want nucleotides, but they just need to grow.The Journal of clinical investigation · 2026Article
- Relapsed rhabdoid tumours and other non-nephroblastoma childhood and adolescent kidney tumours: perspectives from the HARMONICA collaboration.Nature reviews. Urology · 2026Review
- Patient-derived complex organoids are a critical tool to understand and explore pediatric malignant brain tumors.Cancer metastasis reviews · 2026Review
- Exploring metabolic dynamics of cancer metastasis through in vitro models.Discover oncology · 2026Review
- Current treatment landscape and translational priorities in malignant rhabdoid tumor of the kidney.Frontiers in pediatrics · 2026Review
- Multiscale Construction, Evaluation, and Application of Organoids.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Review
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Authors and funding
10 authors.
Funding
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Abstract
Malignant rhabdoid tumor (MRT) is one of the most aggressive childhood cancers for which no effective treatment options are available. Reprogramming of cellular metabolism is an important hallmark of cancer, with various metabolism-based drugs being approved as a cancer treatment. In this study, we use patient-derived tumor organoids (tumoroids) to map the metabolic landscape of several pediatric cancers. Combining gene expression analyses and metabolite profiling using mass spectrometry, we find nucleotide biosynthesis to be a particular vulnerability of MRT. Treatment of MRT tumoroids with de novo nucleotide synthesis inhibitors methotrexate (MTX) and BAY-2402234 lowers nucleotide levels in MRT tumoroids and induces apoptosis. Lastly, we demonstrate in vivo efficacy of MTX in MRT patient-derived xenograft (PDX) mouse models. Our study reveals nucleotide biosynthesis as an MRT-specific metabolic vulnerability, which can ultimately lead to better treatment options for children suffering from this lethal pediatric malignancy.
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Registered trials
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