ArticleNature metabolism2024
Glucose limitation protects cancer cells from apoptosis induced by pyrimidine restriction and replication inhibition.
Article in Nature metabolism, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- A visualizable mitochondrial-targeted Chlorambucil prodrug for enhancing anti-hepatoma efficacy.Pharmaceutical science advances · 2026Article
- Nuclear OXCT1 attenuates histone β-hydroxybutyrylation-mediated MHC-I transcription.Nature chemical biology · 2026Article
- DHODH inhibition drives albumin-mediated drug resistance through TERF2IP lactylation-activated macropinosome-mitochondria contact.Nature communications · 2026Article
- Glucose restriction reprograms lipid metabolism and enhances immunotherapy through ZNRF3-Wnt-SCD signaling axis.Journal for immunotherapy of cancer · 2026Article
- LIFe of the sugar-free party in cancer metabolism.Trends in endocrinology and metabolism: TEM · 2026Article
- Succinate dehydrogenase loss suppresses pyrimidine biosynthesis via succinate-mediated inhibition of aspartate transcarbamylase.Nature metabolism · 2026Article
- Metabolic reprogramming in cancer: dysregulation of glucose, lipid, and amino acid pathways and therapeutic opportunities.Molecular biomedicine · 2026Review
- Nanomedicine-enabled disruption of glucose metabolism and synergistic antitumor therapy.Journal of nanobiotechnology · 2026Review
- Targeting de novo pyrimidine synthesis confers vulnerability to copper-mediated ATR inactivation in PARP inhibitor-resistant ovarian cancer.Nature communications · 2026Article
- Metabolic Subtypes Predict Treatment Response in Acute Myeloid Leukemia: A Pilot Study.Blood and lymphatic cancer : targets and therapy · 2026Article
- A nutrient-responsive cancer-on-chip model for assessing chemotherapy responses under glucose restriction.Frontiers in bioengineering and biotechnology · 2026Article
- Tuned by time: the role of circadian rhythms in metabolic energy sensing and chronotherapy.Annals of medicine · 2025Review
- Heterogeneity sonata: Orchestrating distal metastasis under stress.Journal of the National Cancer Center · 2025Article
- Drug-tolerant persister cells in cancer: bridging the gaps between bench and bedside.Nature communications · 2025Review
- De novo pyrimidine biosynthesis inhibition synergizes with BCL-XNature communications · 2025Article
- Metabolic Adaptations in Cancer Progression: Optimization Strategies and Therapeutic Targets.Cancers · 2025Review
- Silencing PPA1 promotes the survival of non-small cell lung cancer A549 cells under glucose-starved conditions.Translational cancer research · 2025Article
- Radiotherapy-induced alterations in tumor microenvironment: metabolism and immunity.Frontiers in cell and developmental biology · 2025Review
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
Cancer cells often experience nutrient-limiting conditions because of their robust proliferation and inadequate tumour vasculature, which results in metabolic adaptation to sustain proliferation. Most cancer cells rapidly consume glucose, which is severely reduced in the nutrient-scarce tumour microenvironment. In CRISPR-based genetic screens to identify metabolic pathways influenced by glucose restriction, we find that tumour-relevant glucose concentrations (low glucose) protect cancer cells from inhibition of de novo pyrimidine biosynthesis, a pathway that is frequently targeted by chemotherapy. We identify two mechanisms to explain this result, which is observed broadly across cancer types. First, low glucose limits uridine-5-diphosphate-glucose synthesis, preserving pyrimidine nucleotide availability and thereby prolonging the time to replication fork stalling. Second, low glucose directly modulates apoptosis downstream of replication fork stalling by suppressing BAK activation and subsequent cytochrome c release, key events that activate caspase-9-dependent mitochondrial apoptosis. These results indicate that the low glucose levels frequently observed in tumours may limit the efficacy of specific chemotherapeutic agents, highlighting the importance of considering the effects of the tumour nutrient environment on cancer therapy.
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