ArticleCancer cell2022
A druggable addiction to de novo pyrimidine biosynthesis in diffuse midline glioma.
Article in Cancer cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 134 citations in OpenAlex.
- Japanese encephalitis virus reprograms host pyrimidine metabolism to facilitate viral replication.Infectious medicine · 2026Article
- Dynamic control of nucleotide metabolism in physiology and disease.Nature cell biology · 2026Review
- Combined inhibition of de novo pyrimidine synthesis and ATR promotes ATF4-mediated cell death inHemaSphere · 2026Article
- DNA-PKcs inhibition sensitizes glioblastoma to radiotherapy through reprogramming of tumor cell states and immune microenvironment cell types.Research square · 2026Article
- Myricetin InhibitsCells · 2026Article
- Nitrogen metabolism profiling reveals cell state-specific pyrimidine synthesis pathway choice.Nature metabolism · 2026Article
- The oncogenic control of nucleotide synthesis.Oncogenesis · 2026Review
- Metabolic permissiveness: how tissue context shapes cancer.Genes & development · 2026Review
- Epigenetic mechanisms and therapeutic advances in diffuse midline glioma (Review).Oncology reports · 2026Review
- Targeting de novo pyrimidine synthesis confers vulnerability to copper-mediated ATR inactivation in PARP inhibitor-resistant ovarian cancer.Nature communications · 2026Article
- Lactylation fuels nucleotide biosynthesis and facilitates deuterium metabolic imaging of tumor proliferation in preclinical models of H3K27M-mutant gliomas.Science translational medicine · 2026Article
- Stable isotope tracing in human plasma-like medium reveals metabolic and immune modulation of the glioblastoma microenvironment.Neuro-oncology · 2026Article
- Molecular mechanisms and clinical significance of the glioma metabolic-immune axis: a comprehensive review.Frontiers in immunology · 2026Review
- Promising efficacy of teniposide in H3K27M mutant diffuse midline gliomas: a case report.Frontiers in oncology · 2026Article
- Imaging-mediated genetic effects link brain microstructure, metabolic profiles, and regional transcription to glioma susceptibility.Frontiers in immunology · 2026Article
- Identification of pyrimidine metabolism-based molecular subtypes and prognostic signature to predict immune landscape and guide clinical treatment in prostate cancer.Annals of medicine · 2025Article
- Targeting plasticity in the pyrimidine synthesis pathway potentiates macrophage-mediated phagocytosis in pancreatic cancer models.The Journal of clinical investigation · 2025Article
- Recurrent Breast Cancer Cells Depend onbioRxiv : the preprint server for biology · 2025Article
- Decoding Gene Expression Changes in Cerebral Tumors: Before and After Radiotherapy.Medicinal research reviews · 2025Review
- Identifying prognostic targets in metastatic prostate cancer beyond AR.FEBS open bio · 2025Article
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Authors and funding
22 authors at 7 institutions in 1 country.
Funding
Abstract
Diffuse midline glioma (DMG) is a uniformly fatal pediatric cancer driven by oncohistones that do not readily lend themselves to drug development. To identify druggable targets for DMG, we conducted a genome-wide CRISPR screen that reveals a DMG selective dependency on the de novo pathway for pyrimidine biosynthesis. This metabolic vulnerability reflects an elevated rate of uridine/uracil degradation that depletes DMG cells of substrates for the alternate salvage pyrimidine biosynthesis pathway. A clinical stage inhibitor of DHODH (rate-limiting enzyme in the de novo pathway) diminishes uridine-5'-phosphate (UMP) pools, generates DNA damage, and induces apoptosis through suppression of replication forks-an "on-target" effect, as shown by uridine rescue. Matrix-assisted laser desorption/ionization (MALDI) mass spectroscopy imaging demonstrates that this DHODH inhibitor (BAY2402234) accumulates in the brain at therapeutically relevant concentrations, suppresses de novo pyrimidine biosynthesis in vivo, and prolongs survival of mice bearing intracranial DMG xenografts, highlighting BAY2402234 as a promising therapy against DMGs.
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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.