ArticleNature communications2020
Purine metabolism regulates DNA repair and therapy resistance in glioblastoma.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 165 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
165 citing papers in PubMed, 1 synthesis or guideline pooled it, 250 citations in OpenAlex.
- A systematic review of omics discovery studies to identify pertinent metabolic pathways for locally advanced rectal cancer in response to neoadjuvant chemoradiotherapy.Metabolomics : Official journal of the Metabolomic Society · 2025Pooled it
- PTEN-loss confers dependence on the guanylate synthesis enzyme IMPDH in T-cell acute lymphoblastic leukemia.EMBO molecular medicine · 2026Article
- Mitochondrial Metabolic Reprogramming in Glioma: Mechanisms of Tumorigenesis and Implications for Clinical Therapy.CNS neuroscience & therapeutics · 2026Review
- Microenvironment-derived acetylated amino acids promote glioblastoma treatment resistance.Research square · 2026Article
- Construction Strategies, Microenvironmental Modelling and Precision-Therapy Applications of Glioma Organoid Models.Cancers · 2026Review
- Fatty Acid Metabolism Rewires Glioblastoma Progression and Treg-Mediated Immune Resistance.Cancers · 2026Review
- Integrated Proteomic and Metabolomic Analyses of Cerebrospinal Fluid from Pediatric Patients with Diffuse Intrinsic Pontine Glioma.International journal of molecular sciences · 2026Article
- Digital Twins as the Implementation Layer of Precision Medicine in Pediatric Neurosurgery.Journal of Korean Neurosurgical Society · 2026Review
- Amino-acids-mTORC1-driven DDA1 phosphorylation promotes DNA repair and glioblastoma progression.Cell communication and signaling : CCS · 2026Article
- Review
- Mitochondria transfer in glioblastoma.Neuro-oncology · 2026Review
- Modeling blood-brain barrier-glioblastoma interactions: implications for chemoresistance and therapeutic targeting.Fluids and barriers of the CNS · 2026Review
- mTOR inhibition enhances the antitumor efficacy of pan-RAF-MEK blockade by inhibiting the ATF4-MTHFD2 pathway.Cell death & disease · 2026Article
- Purine metabolic adaptation protects the endothelium from disturbed flow-induced DNA damage and atherosclerosis.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Heat Shock Affects Amino Acid Metabolism in Bovine Cumulus Cells and Denuded Oocytes During In Vitro Maturation.Biology · 2026Article
- Single-Cell Metabolic Profiling in a Glioblastoma Coculture Model Using AP-MALDI-Based Mass Spectrometry Imaging.Analytical chemistry · 2026Article
- Liquid-liquid phase separation in cancer therapy resistance.iScience · 2026Review
- Expanding the targeted protein degradation approach with small molecule chimeras directed to the 26S proteasome.Nature communications · 2026Article
- The oncogenic control of nucleotide synthesis.Oncogenesis · 2026Review
- Glioblastoma cells that evade chemoradiotherapy-induced cell death exhibit a bifurcated glycolytic program.Cell death & disease · 2026Article
105 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
28 authors at 4 institutions in 3 countries.
Funding
Abstract
Intratumoral genomic heterogeneity in glioblastoma (GBM) is a barrier to overcoming therapy resistance. Treatments that are effective independent of genotype are urgently needed. By correlating intracellular metabolite levels with radiation resistance across dozens of genomically-distinct models of GBM, we find that purine metabolites, especially guanylates, strongly correlate with radiation resistance. Inhibiting GTP synthesis radiosensitizes GBM cells and patient-derived neurospheres by impairing DNA repair. Likewise, administration of exogenous purine nucleosides protects sensitive GBM models from radiation by promoting DNA repair. Neither modulating pyrimidine metabolism nor purine salvage has similar effects. An FDA-approved inhibitor of GTP synthesis potentiates the effects of radiation in flank and orthotopic patient-derived xenograft models of GBM. High expression of the rate-limiting enzyme of de novo GTP synthesis is associated with shorter survival in GBM patients. These findings indicate that inhibiting purine synthesis may be a promising strategy to overcome therapy resistance in this genomically heterogeneous disease.
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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.