ArticleThe Journal of clinical investigation2022
Creatine riboside is a cancer cell-derived metabolite associated with arginine auxotrophy.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 10 citations in OpenAlex.
- Urinary Metabolites and Survival in Malignant Mesothelioma.medRxiv : the preprint server for health sciences · 2025Article
- The systemic oxidative stress index predicts clinical outcomes of esophageal squamous cell carcinoma receiving neoadjuvant immunochemotherapy.Frontiers in immunology · 2025Article
- Gastric Cancer and Intestinal Metaplasia: Differential Metabolic Landscapes and New Pathways to Diagnosis.International journal of molecular sciences · 2024Article
- Urinary Metabolite Diagnostic and Prognostic Liquid Biopsy Biomarkers of Lung Cancer in Nonsmokers and Tobacco Smokers.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Liquid biopsy techniques and lung cancer: diagnosis, monitoring and evaluation.Journal of experimental & clinical cancer research : CR · 2024Review
- Development and investigation of metabolism-associated risk assessment models for patients with viral hepatitis.Frontiers in cellular and infection microbiology · 2023Article
- Extracellular matrix profiles determine risk and prognosis of the squamous cell carcinoma subtype of non-small cell lung carcinoma.Genome medicine · 2022Article
- Making liver cancer cells go ARGh!The EMBO journal · 2022Article
Corrections and comments
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Authors and funding
20 authors at 5 institutions in 1 country.
Funding
Abstract
The metabolic dependencies of cancer cells have substantial potential to be exploited to improve the diagnosis and treatment of cancer. Creatine riboside (CR) is identified as a urinary metabolite associated with risk and prognosis in lung and liver cancer. However, the source of high CR levels in patients with cancer as well as their implications for the treatment of these aggressive cancers remain unclear. By integrating multiomics data on lung and liver cancer, we have shown that CR is a cancer cell-derived metabolite. Global metabolomics and gene expression analysis of human tumors and matched liquid biopsies, together with functional studies, revealed that dysregulation of the mitochondrial urea cycle and a nucleotide imbalance were associated with high CR levels and indicators of a poor prognosis. This metabolic phenotype was associated with reduced immune infiltration and supported rapid cancer cell proliferation that drove aggressive tumor growth. CRhi cancer cells were auxotrophic for arginine, revealing a metabolic vulnerability that may be exploited therapeutically. This highlights the potential of CR not only as a poor-prognosis biomarker but also as a companion biomarker to inform the administration of arginine-targeted therapies in precision medicine strategies to improve survival for patients with cancer.
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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.