ArticleJournal of experimental & clinical cancer research : CR2014
Pegylated arginine deiminase synergistically increases the cytotoxicity of gemcitabine in human pancreatic cancer.
Article in Journal of experimental & clinical cancer research : CR, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 44 citations in OpenAlex.
- Metabolic plasticity in pancreatic ductal adenocarcinoma progression and response to treatment.Molecular cancer · 2026Review
- Advances in Drug Therapy for Metastatic Pancreatic Ductal Adenocarcinoma.Journal of Cancer · 2024Review
- Ribonucleotide reductase M2 (RRM2): Regulation, function and targeting strategy in human cancer.Genes & diseases · 2024Review
- A comprehensive analysis of ribonucleotide reductase subunit M2 for carcinogenesis in pan-cancer.PloS one · 2024Article
- Unlocking the Potential of Arginine Deprivation Therapy: Recent Breakthroughs and Promising Future for Cancer Treatment.International journal of molecular sciences · 2023Review
- The addition of arginine deiminase potentiates Mithramycin A-induced cell death in patient-derived glioblastoma cells via ATF4 and cytochrome C.Cancer cell international · 2023Article
- Bench-to-Bedside Studies of Arginine Deprivation in Cancer.Molecules (Basel, Switzerland) · 2023Review
- Editorial: New insights into molecular mechanisms and targeted therapy for gastrointestinal tumors.Frontiers in cell and developmental biology · 2023Article
- Article
- Insight into the interplay between mitochondria-regulated cell death and energetic metabolism in osteosarcoma.Frontiers in cell and developmental biology · 2022Review
- Oxidative Stress and X-ray Exposure Levels-Dependent Survival and Metabolic Changes in Murine HSPCs.Antioxidants (Basel, Switzerland) · 2021Article
- Enhancing the Effect of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Signaling and Arginine Deprivation in Melanoma.International journal of molecular sciences · 2021Review
- Arginine Signaling and Cancer Metabolism.Cancers · 2021Review
- Phase I study of ADI-PEG20 plus low-dose cytarabine for the treatment of acute myeloid leukemia.Cancer medicine · 2021Article
- MicroRNA-1291-5p Sensitizes Pancreatic Carcinoma Cells to Arginine Deprivation and Chemotherapy through the Regulation of Arginolysis and Glycolysis.Molecular pharmacology · 2020Article
- Histone deacetylase inhibition is synthetically lethal with arginine deprivation in pancreatic cancers with low argininosuccinate synthetase 1 expression.Theranostics · 2020Article
- Reprogramming of Amino Acid Metabolism in Pancreatic Cancer: Recent Advances and Therapeutic Strategies.Frontiers in oncology · 2020Review
- Exploiting Arginine Auxotrophy with Pegylated Arginine Deiminase (ADI-PEG20) to Sensitize Pancreatic Cancer to Radiotherapy via Metabolic Dysregulation.Molecular cancer therapeutics · 2019Article
- Arginine Starvation and Docetaxel Induce c-Myc-Driven hENT1 Surface Expression to Overcome Gemcitabine Resistance in ASS1-Negative Tumors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
- Comprehensive analysis of differentially expressed circRNAs revealed a ceRNA network in pancreatic ductaladenocarcinoma.Archives of medical science : AMS · 2019Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
backgroundPancreatic ductal adenocarcinoma has proven to be one of the most chemo-resistant among all solid organ malignancies. Several mechanisms of resistance have been described, though few reports of strategies to overcome this chemo-resistance have been successful in restoring sensitivity to the primary chemotherapy (gemcitabine) and enter the clinical treatment arena.
methodsWe examined the ability of cellular arginine depletion through treatment with PEG-ADI to alter in vitro and in vivo cytotoxicity of gemcitabine. The effect on levels of key regulators of gemcitabine efficacy (e.g. RRM2, hENT1, and dCK) were examined.
resultsCombination of PEG-ADI and gemcitabine substantially increases growth arrest, leading to increased tumor response in vivo. PEG-ADI is a strong inhibitor of the gemcitabine-induced overexpression of ribonucleotide reductase subunit M2 (RRM2) levels both in vivo and in vitro, which is associated with gemcitabine resistance. This mechanism is through the abrogation of the gemcitabine-mediated inhibitory effect on E2F-1 function, a transcriptional repressor of RRM2.
conclusionThe ability to alter gemcitabine resistance in a targeted manner by inducing metabolic stress holds great promise in the treatment of advanced pancreatic 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.