ArticleOncogene2022
DHODH inhibition impedes glioma stem cell proliferation, induces DNA damage, and prolongs survival in orthotopic glioblastoma xenografts.
Article in Oncogene, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
26 citing papers in PubMed, 28 citations in OpenAlex.
- Mitochondrial Metabolic Reprogramming in Glioma: Mechanisms of Tumorigenesis and Implications for Clinical Therapy.CNS neuroscience & therapeutics · 2026Review
- An integrative multi-omics landscape of multi-dimensional cellular stress and metabolic reprogramming in melanoma treated with targeted alpha therapy.Journal of nanobiotechnology · 2026Article
- Mitochondria transfer in glioblastoma.Neuro-oncology · 2026Review
- DHODH inhibition suppresses cutaneous squamous cell carcinoma growth by the induction of differentiation through perturbation of the cellular redox balance.Cell death & disease · 2026Article
- Mitochondrial Transfer Rescues Respiration to Support De Novo Pyrimidine Biosynthesis and Tumor Progression.Cancer research · 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
- Systemic cyst(e)inase administration induces ferroptosis and synergizes with temozolomide in glioblastoma.iScience · 2026Article
- Molecular mechanisms and clinical significance of the glioma metabolic-immune axis: a comprehensive review.Frontiers in immunology · 2026Review
- Metabolic reprogramming and immunosenescence: a new sight for glioma therapy.Frontiers in cell and developmental biology · 2026Review
- TP53-dependent antitumor effects of DHODH Inhibition in nasopharyngeal carcinoma.Discover oncology · 2025Article
- Article
- DHODH modulates immune evasion of cancer cells via CDP-Choline dependent regulation of phospholipid metabolism and ferroptosis.Nature communications · 2025Article
- Metabolic reprogramming in glioblastoma: a rare case of recurrence to scalp metastasis.BJC reports · 2025Article
- Metabolism and signaling crosstalk in glioblastoma progression and therapy resistance.Molecular oncology · 2025Review
- Malignant Cells Beyond the Tumor Core: The Non-Negligible Factor to Overcome the Refractory of Glioblastoma.CNS neuroscience & therapeutics · 2025Review
- Metabolic shifts in glioblastoma: unraveling altered pathways and exploring novel therapeutic avenues.Molecular biology reports · 2025Review
- Metabolic profiling of patient-derived organoids reveals nucleotide synthesis as a metabolic vulnerability in malignant rhabdoid tumors.Cell reports. Medicine · 2025Article
- Targeting metabolic reprogramming in glioblastoma as a new strategy to overcome therapy resistance.Frontiers in cell and developmental biology · 2025Review
- Metabolic Reprogramming in Glioblastoma Multiforme: A Review of Pathways and Therapeutic Targets.Cells · 2024Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Glioma stem cells (GSCs) promote tumor progression and therapeutic resistance and exhibit remarkable bioenergetic and metabolic plasticity, a phenomenon that has been linked to their ability to escape standard and targeted therapies. However, specific mechanisms that promote therapeutic resistance have been somewhat elusive. We hypothesized that because GSCs proliferate continuously, they may require the salvage and de novo nucleotide synthesis pathways to satisfy their bioenergetic needs. Here, we demonstrate that GSCs lacking EGFR (or EGFRvIII) amplification are exquisitely sensitive to de novo pyrimidine synthesis perturbations, while GSCs that amplify EGFR are utterly resistant. Furthermore, we show that EGFRvIII promotes BAY2402234 resistance in otherwise BAY2402234 responsive GSCs. Remarkably, a novel, orally bioavailable, blood-brain-barrier penetrating, dihydroorotate dehydrogenase (DHODH) inhibitor BAY2402234 was found to abrogate GSC proliferation, block cell-cycle progression, and induce DNA damage and apoptosis. When dosed daily by oral gavage, BAY2402234 significantly impaired the growth of two different intracranial human glioblastoma xenograft models in mice. Given this observed efficacy and the previously established safety profiles in preclinical animal models and human clinical trials, the clinical testing of BAY2402234 in patients with primary glioblastoma that lacks EGFR amplification is warranted.
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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.