ArticleJCI insight2022
DHODH is an independent prognostic marker and potent therapeutic target in neuroblastoma.
Article in JCI insight, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 38 citations in OpenAlex.
- Context matters for drug targeting.Nature chemical biology · 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
- Lactate-driven pyrimidine synthesis promotes ferroptosis resistance in hepatocellular carcinoma.Molecular biomedicine · 2026Article
- Synthetic lethality between RB-loss and E2F3 inhibition in small cell cancers targeted by pyrimidine synthesis blockade.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Antibody‒drug conjugates with DHODH inhibitor as novel payload class for cancer and SARS-CoV-2 infection therapies.Acta pharmaceutica Sinica. B · 2026Article
- Metabolic Dependency on De Novo Pyrimidine Synthesis Is a Targetable Vulnerability in Platinum-Resistant Ovarian Cancer.Cancer research · 2026Article
- A mitochondrial regulatory network of ferroptosis defense in HPV-positive cervical cancer: therapeutic implications of the mitoSTAT3-DHODH axis.Frontiers in pharmacology · 2026Review
- Advances in multi-omics research on neuroblastoma.Frontiers in pediatrics · 2026Review
- Review
- Targeting Pathways in Neuroblastoma: Advances in Treatment Strategies and Clinical Outcomes.International journal of molecular sciences · 2025Review
- Comparative Single-Cell Transcriptomics of Human Neuroblastoma and Preclinical Models Reveals Conservation of an Adrenergic Cell State.Cancer research · 2025Article
- Study of an N6-methyladenosine- and ferroptosis-related prognostic model and the mechanisms underlying the molecular network in neuroblastoma based on multiple datasets.Discover oncology · 2025Article
- Carbon-ion radiotherapy induces ferroptosis and M1 macrophage polarization to inhibit the development of gastric cancer by downregulating DHODH.Frontiers in medicine · 2025Article
- Molecular regulation and therapeutic targeting ofFrontiers in cell and developmental biology · 2025Review
- DHODH Inhibition SuppressesCancers · 2024Article
- Defining neuroblastoma: From origin to precision medicine.Neuro-oncology · 2024Review
- Ginsenoside RK1 Induces Ferroptosis in Hepatocellular Carcinoma Cells through an FSP1-Dependent Pathway.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Bioinformatics analysis and experimental verification of the cancer-promoting effect of DHODH in clear cell renal cell carcinoma.Scientific reports · 2024Article
- Article
Corrections and comments
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Authors and funding
17 authors at 5 institutions in 3 countries.
Funding
Abstract
Despite intensive therapy, children with high-risk neuroblastoma are at risk of treatment failure. We applied a multiomic system approach to evaluate metabolic vulnerabilities in human neuroblastoma. We combined metabolomics, CRISPR screening, and transcriptomic data across more than 700 solid tumor cell lines and identified dihydroorotate dehydrogenase (DHODH), a critical enzyme in pyrimidine synthesis, as a potential treatment target. Of note, DHODH inhibition is currently under clinical investigation in patients with hematologic malignancies. In neuroblastoma, DHODH expression was identified as an independent risk factor for aggressive disease, and high DHODH levels correlated to worse overall and event-free survival. A subset of tumors with the highest DHODH expression was associated with a dismal prognosis, with a 5-year survival of less than 10%. In xenograft and transgenic neuroblastoma mouse models treated with the DHODH inhibitor brequinar, tumor growth was dramatically reduced, and survival was extended. Furthermore, brequinar treatment was shown to reduce the expression of MYC targets in 3 neuroblastoma models in vivo. A combination of brequinar and temozolomide was curative in the majority of transgenic TH-MYCN neuroblastoma mice, indicating a highly active clinical combination therapy. Overall, DHODH inhibition combined with temozolomide has therapeutic potential in neuroblastoma, and we propose this combination for clinical testing.
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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.