ArticleCell reports2016
Inhibition of the Polyamine Synthesis Pathway Is Synthetically Lethal with Loss of Argininosuccinate Synthase 1.
Article in Cell reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 57 citations in OpenAlex.
- Immunotherapy resistance and strategies in malignant pleural mesothelioma.Cancer drug resistance (Alhambra, Calif.) · 2026Review
- Molecular mechanisms and therapies for tumor inhibition through the arginine metabolism pathway.Frontiers in oncology · 2026Review
- Polyamine metabolism in cancer: drivers of immune evasion, ferroptosis and therapy resistance.Expert reviews in molecular medicine · 2025Review
- Endothelial Arginine Metabolism in Angiogenesis: Mechanistic Insights from Tissue Repair to Tumor Progression.Metabolites · 2025Review
- Two types of covering crops are beneficial to improve the nitrogen metabolism of Citrus roots.BMC plant biology · 2025Article
- Etoposide-induced protein 2.4 homolog promotes argininosuccinate synthase 1 and cancer cell survival upon arginine deprivation.Cellular & molecular biology letters · 2025Article
- Overcoming resistance to arginine deprivation therapy using GC7 in pleural mesothelioma.iScience · 2025Article
- The Synergistic Benefit of Combination Strategies Targeting Tumor Cell Polyamine Homeostasis.International journal of molecular sciences · 2024Review
- Targeted Approaches to Treatment of Pleural Mesothelioma: A Review.JCO precision oncology · 2023Review
- Unlocking the Potential of Arginine Deprivation Therapy: Recent Breakthroughs and Promising Future for Cancer Treatment.International journal of molecular sciences · 2023Review
- A role for macrophages under cytokine control in mediating resistance to ADI-PEG20 (pegargiminase) in ASS1-deficient mesothelioma.Pharmacological reports : PR · 2023Article
- Article
- A pan-cancer analysis of the role of argininosuccinate synthase 1 in human tumors.Frontiers in oncology · 2023Article
- Metabolomic and Transcriptomic Profiling Identified Significant Genes in Thymic Epithelial Tumor.Metabolites · 2022Article
- Pegylated arginine deiminase drives arginine turnover and systemic autophagy to dictate energy metabolism.Cell reports. Medicine · 2022Article
- Argininosuccinate synthase 1, arginine deprivation therapy and cancer management.Frontiers in pharmacology · 2022Review
- Arginine Deprivation in SCLC: Mechanisms and Perspectives for Therapy.Lung Cancer (Auckland, N.Z.) · 2022Review
- Arginine Signaling and Cancer Metabolism.Cancers · 2021Review
- Polyamine Homeostasis in Development and Disease.Medical sciences (Basel, Switzerland) · 2021Review
- Naturally-occurring spinosyn A and its derivatives function as argininosuccinate synthase activator and tumor inhibitor.Nature communications · 2021Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
Argininosuccinate synthase 1 (ASS1) is the rate-limiting enzyme for arginine biosynthesis. ASS1 expression is lost in a range of tumor types, including 50% of malignant pleural mesotheliomas. Starving ASS1-deficient cells of arginine with arginine blockers such as ADI-PEG20 can induce selective lethality and has shown great promise in the clinical setting. We have generated a model of ADI-PEG20 resistance in mesothelioma cells. This resistance is mediated through re-expression of ASS1 via demethylation of the ASS1 promoter. Through coordinated transcriptomic and metabolomic profiling, we have shown that ASS1-deficient cells have decreased levels of acetylated polyamine metabolites, together with a compensatory increase in the expression of polyamine biosynthetic enzymes. Upon arginine deprivation, polyamine metabolites are decreased in the ASS1-deficient cells and in plasma isolated from ASS1-deficient mesothelioma patients. We identify a synthetic lethal dependence between ASS1 deficiency and polyamine metabolism, which could potentially be exploited for the treatment of ASS1-negative cancers.
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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.