ArticleScience translational medicine2019
Targeting pyrimidine synthesis accentuates molecular therapy response in glioblastoma stem cells.
Article in Science translational medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 129 papers, 2 of them syntheses that pooled it.
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Who cites it
129 citing papers in PubMed, 2 syntheses or guidelines pooled it, 198 citations in OpenAlex.
- Biomarkers Identification in the Microenvironment of Oral Squamous Cell Carcinoma: A Systematic Review of Proteomic Studies.International journal of molecular sciences · 2024Pooled it
- Systematic Review of Molecular Targeted Therapies for Adult-Type Diffuse Glioma: An Analysis of Clinical and Laboratory Studies.International journal of molecular sciences · 2023Pooled it
- Pharmacologically Targeting DHODH-Dependent Pyrimidine Metabolism with HSA-Conjugated BRQ Suppresses Leukemogenesis.Cancers · 2026Article
- Gliomas phenocopy an inborn error of metabolism to drive neuronal activity and tumor growth.Cell · 2026Article
- Cancer stem cells synthesize proline to attenuate oxidative stress.The Journal of clinical investigation · 2026Article
- A Pan-Cancer Multi-Omics Analysis of CAD: Integrating CRISPR and Metabolomics Data to Unravel the Metabolic-Immune Axis and Immunotherapy Response.Biomedicines · 2026Article
- PLSCR1 drives chemoresistance in TNBC via METTL3/IGF2BP3-mediated mRNA stabilization and EGFR-MAPK pathway activation.Cell death & disease · 2026Article
- Nitrogen metabolism profiling reveals cell state-specific pyrimidine synthesis pathway choice.Nature metabolism · 2026Article
- DHODH inhibition suppresses cutaneous squamous cell carcinoma growth by the induction of differentiation through perturbation of the cellular redox balance.Cell death & disease · 2026Article
- Glioblastoma cells that evade chemoradiotherapy-induced cell death exhibit a bifurcated glycolytic program.Cell death & disease · 2026Article
- Article
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- Acetyl-CoA synthase 1 mediates metabolic reprogramming to promote proliferation and metastasis of osteosarcoma.Journal of orthopaedic translation · 2026Article
- Structural and molecular basis for allosteric regulation and catalytic coupling of human phosphoribosylformylglycinamidine synthase.Nature communications · 2026Article
- Stable isotope tracing in human plasma-like medium reveals metabolic and immune modulation of the glioblastoma microenvironment.Neuro-oncology · 2026Article
- Potential oncogene VPS72 in hepatocellular carcinoma: prognostic and immune infiltration implications.European journal of medical research · 2026Article
- Highlighting the Therapeutic Potential of an Underexplored Target: Human Dihydroorotate Dehydrogenase in Cancer, Rheumatoid Arthritis and Sclerosis.Current topics in medicinal chemistry · 2026Review
- Simian iPS-derived hepatocytes supportFrontiers in cellular and infection microbiology · 2026Article
- BioLM-NET: an interpretable deep learning model combining prior biological knowledge and contextual LLM gene embeddings on multi-omics data to predict disease.Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing · 2026Article
- Uridine 5'-monophosphate (UMP) synthesis connects nucleotide metabolism to programmed cell death in C. elegans.Cell death and differentiation · 2026Article
69 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
22 authors at 7 institutions in 2 countries.
Funding
Abstract
Glioblastoma stem cells (GSCs) reprogram glucose metabolism by hijacking high-affinity glucose uptake to survive in a nutritionally dynamic microenvironment. Here, we trace metabolic aberrations in GSCs to link core genetic mutations in glioblastoma to dependency on de novo pyrimidine synthesis. Targeting the pyrimidine synthetic rate-limiting step enzyme carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, dihydroorotase (CAD) or the critical downstream enzyme dihydroorotate dehydrogenase (DHODH) inhibited GSC survival, self-renewal, and in vivo tumor initiation through the depletion of the pyrimidine nucleotide supply in rodent models. Mutations in EGFR or PTEN generated distinct CAD phosphorylation patterns to activate carbon influx through pyrimidine synthesis. Simultaneous abrogation of tumor-specific driver mutations and DHODH activity with clinically approved inhibitors demonstrated sustained inhibition of metabolic activity of pyrimidine synthesis and GSC tumorigenic capacity in vitro. Higher expression of pyrimidine synthesis genes portends poor prognosis of patients with glioblastoma. Collectively, our results demonstrate a therapeutic approach of precision medicine through targeting the nexus between driver mutations and metabolic reprogramming in cancer stem cells.
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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.