ArticleMolecular cancer therapeutics2019
Exploiting Arginine Auxotrophy with Pegylated Arginine Deiminase (ADI-PEG20) to Sensitize Pancreatic Cancer to Radiotherapy via Metabolic Dysregulation.
Article in Molecular cancer therapeutics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 36 citations in OpenAlex.
- A pharmacodynamic study of rapid lactate metabolic modulation by intravenous L-arginine in brain metastases.Frontiers in oncology · 2026Trial
- Metabolic plasticity in pancreatic ductal adenocarcinoma progression and response to treatment.Molecular cancer · 2026Review
- Synergistic effects of L-arginine and argininosuccinate synthetase 1 in inducing apoptosis in hepatocellular carcinoma.Journal of liver cancer · 2025Article
- Sestrin3 confers resistance to recombinant human arginase in small cell lung cancer by activating Akt/mTOR/ASS1 axis.PloS one · 2025Article
- Sphingolipid Metabolism Dysregulation Drives Immune Microenvironment Remodeling and Predicts Prognosis in Bladder Cancer.International journal of genomics · 2025Article
- Demystifying metabolic‒immune crosstalk: how amino acid metabolic reprogramming shapes the malignant phenotype and macrophage polarization of biliary and pancreatic tumors.International journal of biological sciences · 2025Review
- Metabolic-Modulating Effects of Radiation: Undetectable Yet Deadly-A Review on Radiotherapy.Cancers · 2024Review
- Advances in Drug Therapy for Metastatic Pancreatic Ductal Adenocarcinoma.Journal of Cancer · 2024Review
- Unlocking the Potential of Arginine Deprivation Therapy: Recent Breakthroughs and Promising Future for Cancer Treatment.International journal of molecular sciences · 2023Review
- Novel insight into metabolic reprogrammming in cancer radioresistance: A promising therapeutic target in radiotherapy.International journal of biological sciences · 2023Review
- Metabolic response to radiation therapy in cancer.Molecular carcinogenesis · 2022Review
- Targeting Nutrient Dependency in Cancer Treatment.Frontiers in oncology · 2022Review
- Argininosuccinate synthase 1, arginine deprivation therapy and cancer management.Frontiers in pharmacology · 2022Review
- Evaluation of aliphatic acid metabolism in bladder cancer with the goal of guiding therapeutic treatment.Frontiers in oncology · 2022Article
- The metabolic adaptation evoked by arginine enhances the effect of radiation in brain metastases.Science advances · 2021Article
- The prognostic and therapeutic implications of distinct patterns of argininosuccinate synthase 1 (ASS1) and arginase-2 (ARG2) expression by cancer cells and tumor stroma in non-small-cell lung cancer.Cancer & metabolism · 2021Article
- Arginine Signaling and Cancer Metabolism.Cancers · 2021Review
- A Glimpse in the Future of Malignant Mesothelioma Treatment.Frontiers in pharmacology · 2021Review
- Targeting the Integrated Stress Response in Cancer Therapy.Frontiers in pharmacology · 2021Review
- Metabolic Rewiring in Radiation Oncology Toward Improving the Therapeutic Ratio.Frontiers in oncology · 2021Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Distinct metabolic vulnerabilities of cancer cells compared with normal cells can potentially be exploited for therapeutic targeting. Deficiency of argininosuccinate synthetase-1 (ASS1) in pancreatic cancers creates auxotrophy for the semiessential amino acid arginine. We explored the therapeutic potential of depleting exogenous arginine via pegylated arginine deiminase (ADI-PEG20) treatment as an adjunct to radiotherapy. We evaluated the efficacy of treatment of human pancreatic cancer cell lines and xenografts with ADI-PEG20 and radiation via clonogenic assays and tumor growth delay experiments. We also investigated potential mechanisms of action using reverse-phase protein array, Western blotting, and IHC and immunofluorescence staining. ADI-PEG20 potently radiosensitized ASS1-deficient pancreatic cancer cells (MiaPaCa-2, Panc-1, AsPc-1, HPAC, and CaPan-1), but not ASS1-expressing cell lines (Bxpc3, L3.6pl, and SW1990). Reverse phase protein array studies confirmed increased expression of proteins related to endoplasmic reticulum (ER) stress and apoptosis, which were confirmed by Western blot analysis. Inhibition of ER stress signaling with 4-phenylbutyrate abrogated the expression of ER stress proteins and reversed radiosensitization by ADI-PEG20. Independent
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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 Socratic graph.