ArticleAmerican journal of cancer research2023
A novel combination therapy of arginine deiminase and an arginase inhibitor targeting arginine metabolism in the tumor and immune microenvironment.
Article in American journal of cancer research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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The trial behind it
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Who cites it
20 citing papers in PubMed, 13 citations in OpenAlex.
- Amino Acid Metabolism in Health and Disease.MedComm · 2026Review
- Paeoniflorin Ameliorates Alcohol-Induced Depression via Modulating the Gut-Brain Axis and Inhibiting the NF-κB/NLRP3 Inflammasome Pathway in Mice.Phytotherapy research : PTR · 2026Article
- From guardians to traitors: molecular mechanisms of tumor-induced T cell betrayal.Molecular cancer · 2026Review
- Review
- Immune modulatory vaccines targeting tumor microenvironment antigens: recent advances in oncology and beyond.Signal transduction and targeted therapy · 2026Review
- Metabolic networks in the tumor microenvironment: roles of amino acid and lipid metabolism pathways in cancer progression and therapy.Experimental & molecular medicine · 2026Review
- The role of L-Arginine metabolism in the hallmarks of cancer as an emerging pathway to drug design.Frontiers in pharmacology · 2026Review
- Comprehensive characterization of AP-1 adaptor complex genes in lung cancer reveals AP1AR as a novel prognostic and therapeutic biomarker.Journal of Cancer · 2026Article
- Multi-Omics and Single-Cell Dissection of Exostosin Glycosyltransferases (EXT1/EXT2) Reveals Divergent Oncogenic Roles and Therapeutic Vulnerabilities in Gliomas.Journal of Cancer · 2026Article
- Single-cell and transcriptomic profiling reveal stemness-driven immune evasion in obstructive sleep apnea (OSA) associated lung cancer.Journal of Cancer · 2026Article
- The Multi-dimensional Mechanisms and Transformation Prospects of the Intratumoral Microbiota-Arginine Metabolism Axis in Tumor Progression and Immune Regulation.International journal of medical sciences · 2026Review
- Metal ion transporter SLC39A14-mediated ferroptosis and glycosylation modulate the tumor immune microenvironment: pan-cancer multi-omics exploration of therapeutic potential.Cancer cell international · 2025Article
- Immunometabolism: crosstalk with tumor metabolism and implications for cancer immunotherapy.Molecular cancer · 2025Review
- Current advancement of immune function paradox of tumour-infiltrating cells and their immunotherapeutic targets: a mini-review.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Identification of candidate proteins influencing spermatogenesis in Shandong black cattle via integrated multiomics analysis.BMC genomics · 2025Article
- Metabolomic reprogramming of the tumor microenvironment by dual arginase inhibitor OATD-02 boosts anticancer immunity.Scientific reports · 2025Article
- Therapeutic potential of natural arginase modulators: mechanisms, challenges, and future directions.Frontiers in pharmacology · 2025Review
- Regulation of dendritic cell biology by amino acids and their transporters.Frontiers in immunology · 2025Review
- Enhanced anti-cancer efficacy of arginine deaminase expressed by tumor-seeking Salmonella Gallinarum.Oncogene · 2024Article
- Comprehensive analysis of bulk and single-cell RNA sequencing data reveals Schlafen-5 (SLFN5) as a novel prognosis and immunity.International journal of medical sciences · 2024Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tumor progression is dependent on tumor cells and their microenvironment. It is important to identify therapies that inhibit cancer cells and activate immune cells. Arginine modulation plays a dual role in cancer therapy. Arginase inhibition induced an anti-tumor effect via T-cell activation through an increase in arginine in the tumor environment. In contrast, arginine depletion by arginine deiminase pegylated with 20,000-molecular-weight polyethylene glycol (ADI-PEG 20) induced an anti-tumor response in argininosuccinate synthase 1 (ASS1)-deficient tumor cells. ADI-PEG 20 did not cause toxicity to normal immune cells, which can recycle the ADI-degraded product citrulline back to arginine. To target tumor cells and their neighboring immune cells, we hypothesized that the combination of an arginase inhibitor (L-Norvaline) and ADI-PEG 20 may trigger a stronger anticancer response. In this study, we found that L-Norvaline inhibits tumor growth in vivo. Pathway analysis based on RNA-seq data indicated that the differentially expressed genes (DEGs) were significantly enriched in some immune-related pathways. Significantly, L-Norvaline did not inhibit tumor growth in immunodeficient mice. In addition, combination treatment with L-Norvaline and ADI-PEG 20 induced a more robust anti-tumor response against B16F10 melanoma. Furthermore, single-cell RNA-seq data demonstrated that the combination therapy increased tumor-infiltrating CD8
Indexed as
Identifiers
37293150PMC10244097W4379967499What Socratic holds
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 Socratic graph.