ArticleOncotarget2015
Targeting argininosuccinate synthetase negative melanomas using combination of arginine degrading enzyme and cisplatin.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
26 citing papers in PubMed, 41 citations in OpenAlex.
- Trial
- Targeting arginine metabolism overcomes chemotherapy resistance in aggressive-variant prostate cancers.iScience · 2026Article
- Extract ofToxins · 2025Article
- Unlocking the Potential of Arginine Deprivation Therapy: Recent Breakthroughs and Promising Future for Cancer Treatment.International journal of molecular sciences · 2023Review
- Regulated Arginine Metabolism in Immunopathogenesis of a Wide Range of Diseases: Is There a Way to Pass between Scylla and Charybdis?Current issues in molecular biology · 2023Review
- Bench-to-Bedside Studies of Arginine Deprivation in Cancer.Molecules (Basel, Switzerland) · 2023Review
- A Phase 1 study of ADI-PEG20 (pegargiminase) combined with cisplatin and pemetrexed in ASS1-negative metastatic uveal melanoma.Pigment cell & melanoma research · 2022Article
- Overcoming Radiation Resistance in Gliomas by Targeting Metabolism and DNA Repair Pathways.International journal of molecular sciences · 2022Review
- Phase 1 trial of ADI-PEG 20 and liposomal doxorubicin in patients with metastatic solid tumors.Cancer medicine · 2022Article
- Arginine depriving enzymes: applications as emerging therapeutics in cancer treatment.Cancer chemotherapy and pharmacology · 2021Review
- 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
- Arginine is an epigenetic regulator targeting TEAD4 to modulate OXPHOS in prostate cancer cells.Nature communications · 2021Article
- Phase 1 trial of ADI-PEG20 plus cisplatin in patients with pretreated metastatic melanoma or other advanced solid malignancies.British journal of cancer · 2021Article
- Genome-wide CRISPR/Cas9 knockout screening uncovers a novel inflammatory pathway critical for resistance to arginine-deprivation therapy.Theranostics · 2021Article
- Collaboration Between RSK-EphA2 and Gas6-Axl RTK Signaling in Arginine Starvation Response That Confers Resistance to EGFR Inhibitors.Translational oncology · 2020Article
- The Janus-like role of proline metabolism in cancer.Cell death discovery · 2020Review
- Exploiting Arginine Auxotrophy with Pegylated Arginine Deiminase (ADI-PEG20) to Sensitize Pancreatic Cancer to Radiotherapy via Metabolic Dysregulation.Molecular cancer therapeutics · 2019Article
- A phase 1 study of ADI-PEG 20 and modified FOLFOX6 in patients with advanced hepatocellular carcinoma and other gastrointestinal malignancies.Cancer chemotherapy and pharmacology · 2018Article
- Sensitivity of Colorectal Cancer to Arginine Deprivation Therapy is Shaped by Differential Expression of Urea Cycle Enzymes.Scientific reports · 2018Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
Loss of argininosuccinate synthetase (ASS) expression in melanoma makes these tumor cells vulnerable to arginine deprivation. Pegylated arginine deiminase (ADI-PEG20) which degrades arginine to citrulline and ammonia has been used clinically and partial responses and stable disease have been noted with minimal toxicity. In order to improve the therapeutic efficacy of ADI-PEG20, we have combined ADI-PEG20 with a DNA damaging agent, cisplatin. We have shown that the combination of the two drugs together significantly improved the therapeutic efficacy when compared to ADI-PEG20 alone or cisplatin alone in 4 melanoma cell lines, regardless of their BRAF mutation. In-vivo study also exhibited the same effect as in-vitro with no added toxicity to either agent alone. The underlying mechanism is complex, but increased DNA damage upon arginine deprivation due to decreased DNA repair proteins, FANCD2, ATM, and CHK1/2 most likely leads to increased apoptosis. This action is further intensified by increased proapoptotic protein, NOXA, and decreased antiapoptotic proteins, SURVIVIN, BCL2 and XIAP. The autophagic process which protects cells from apoptosis upon ADI-PEG20 treatment also dampens upon cisplatin administration. Thus, the combination of arginine deprivation and cisplatin function in concert to kill tumor cells which do not express ASS without added toxicity to normal cells.
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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.