ReviewPharmaceuticals (Basel, Switzerland)2021
Targeting the Proline-Glutamine-Asparagine-Arginine Metabolic Axis in Amino Acid Starvation Cancer Therapy.
Review in Pharmaceuticals (Basel, Switzerland), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 74 citations in OpenAlex.
- Spatial Association Between Polyamine Metabolism and Lipid Peroxidation in Different Pathological Regions of Glioblastoma.Biomedicines · 2026Article
- The MAPK/ATF3/ASNS axis drives amino acid metabolic reprogramming to promote NSCLC survival under glucose deprivation.Journal of translational medicine · 2026Article
- Exploring CHO cell stability during prolonged passaging via eXplainable AI driven flux balance analysis.NPJ systems biology and applications · 2026Article
- The role of L-Arginine metabolism in the hallmarks of cancer as an emerging pathway to drug design.Frontiers in pharmacology · 2026Review
- Amino Acid Metabolism in Chronic Liver Disease: from Pathogenic Driver to Therapeutic Target.International journal of biological sciences · 2026Review
- Metabolic profiles of squamous cell lung carcinoma and diagnostic model construction.Scientific reports · 2025Article
- Revolutionizing cancer treatment with Halomonas Aquamarina L-Glutaminase: insights from in vitro and computational studies.Scientific reports · 2025Article
- Adaptation to Arginine Deprivation Leads to a More Aggressive, Therapy-Resistant Phenotype in HNSCC Cells.Biomolecules · 2025Article
- Exploring Escherichia coli EGY Type II L-Asparaginase Variant of Unique Glutaminase Activity: Cloning, Expression, Biochemical Characterization, and Molecular Docking Analysis.Current microbiology · 2025Article
- Metabolomic Profiling of Disease Progression Following Radiotherapy for Breast Cancer.Cancers · 2025Article
- Marine-derived L-asparaginase: unlocking marine power in anti-tumor therapeutics.Frontiers in immunology · 2025Review
- Endothelial Unfolded Protein Response-Mediated Cytoskeletal Effects.Cell biochemistry and function · 2024Review
- Targeting the glutamine-arginine-proline metabolism axis in cancer.Journal of enzyme inhibition and medicinal chemistry · 2024Review
- Preoperative profiles of plasma amino acids and derivatives distinguish periampullary cancer and benign disease.BMC cancer · 2024Article
- Analysis ofHeliyon · 2024Article
- Exploring the causal relationship between glutamine metabolism and leukemia risk: a Mendelian randomization and LC-MS/MS analysis.Frontiers in immunology · 2024Article
- Metabolomics Analysis Reveals Altered Metabolic Pathways and Response to Doxorubicin in Drug-Resistant Triple-Negative Breast Cancer Cells.Metabolites · 2023Article
- Effects of Date Palm Waste Compost Application on Root Proteome Changes of Barley (Plants (Basel, Switzerland) · 2023Article
- Article
- Association of amino acids and parameters of bone metabolism with endothelial dysfunction and vasculopathic changes in limited systemic sclerosis.Frontiers in medicine · 2023Article
Corrections and comments
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Authors and funding
4 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Proline, glutamine, asparagine, and arginine are conditionally non-essential amino acids that can be produced in our body. However, they are essential for the growth of highly proliferative cells such as cancers. Many cancers express reduced levels of these amino acids and thus require import from the environment. Meanwhile, the biosynthesis of these amino acids is inter-connected but can be intervened individually through the inhibition of key enzymes of the biosynthesis of these amino acids, resulting in amino acid starvation and cell death. Amino acid starvation strategies have been in various stages of clinical applications. Targeting asparagine using asparaginase has been approved for treating acute lymphoblastic leukemia. Targeting glutamine and arginine starvations are in various stages of clinical trials, and targeting proline starvation is in preclinical development. The most important obstacle of these therapies is drug resistance, which is mostly due to reactivation of the key enzymes involved in biosynthesis of the targeted amino acids and reprogramming of compensatory survival pathways via transcriptional, epigenetic, and post-translational mechanisms. Here, we review the interactive regulatory mechanisms that control cellular levels of these amino acids for amino acid starvation therapy and how drug resistance is evolved underlying treatment failure.
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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.