ArticleBritish journal of cancer2012
Negative argininosuccinate synthetase expression in melanoma tumours may predict clinical benefit from arginine-depleting therapy with pegylated arginine deiminase.
Article in British journal of cancer, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00450372 (Clinical Protocol for Phase II Testing of ADI-PEG 20 in Patients With Metastatic Melanoma), which is not on this map. Cited by 58 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Clinical Protocol for Phase II Testing of ADI-PEG 20 in Patients With Metastatic Melanoma
Who cites it
58 citing papers in PubMed, 111 citations in OpenAlex.
- A Phase II Study of Arginine Deiminase (ADI-PEG20) in Relapsed/Refractory or Poor-Risk Acute Myeloid Leukemia Patients.Scientific reports · 2017Trial
- Phase I/II study of pegylated arginine deiminase (ADI-PEG 20) in patients with advanced melanoma.Investigational new drugs · 2013Trial
- Arginine deprivation induces prolonged autophagy activation and ROS-dependent cell death in glioblastoma multiforme.CNS oncology · 2026Article
- Arginine deprivation induces ROS dependent autophagic cell death in human acute myeloid leukemia cells.Human cell · 2026Article
- Energetics of whole genome doubling and genomic instability.Cancer letters · 2025Review
- Research progress on the role of cationic amino acid transporter (CAT) family members in malignant tumors and immune microenvironment.Amino acids · 2023Review
- Unlocking the Potential of Arginine Deprivation Therapy: Recent Breakthroughs and Promising Future for Cancer Treatment.International journal of molecular sciences · 2023Review
- Dietary Manipulation of Amino Acids for Cancer Therapy.Nutrients · 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
- Deregulated Metabolic Pathways in Ovarian Cancer: Cause and Consequence.Metabolites · 2023Review
- Next generation oncolytic viruses expressing PADI1 and TIMP2 exhibit anti-tumor activity against melanoma in nude and humanized mouse models.Molecular therapy oncolytics · 2023Article
- Bench-to-Bedside Studies of Arginine Deprivation in Cancer.Molecules (Basel, Switzerland) · 2023Review
- A novel combination therapy of arginine deiminase and an arginase inhibitor targeting arginine metabolism in the tumor and immune microenvironment.American journal of cancer research · 2023Article
- Amino Acids in Cancer and Cachexia: An Integrated View.Cancers · 2022Review
- Mono-PEGylated thermostable Bacillus caldovelox arginase mutant (BCA-M-PEG20) induces apoptosis, autophagy, cell cycle arrest and growth inhibition in gastric cancer cells.Investigational new drugs · 2022Article
- A Phase 1 study of ADI-PEG20 (pegargiminase) combined with cisplatin and pemetrexed in ASS1-negative metastatic uveal melanoma.Pigment cell & melanoma research · 2022Article
- Phase 1 trial of ADI-PEG 20 and liposomal doxorubicin in patients with metastatic solid tumors.Cancer medicine · 2022Article
- Arginine Deprivation in SCLC: Mechanisms and Perspectives for Therapy.Lung Cancer (Auckland, N.Z.) · 2022Review
- L-Lysine α-Oxidase: Enzyme with Anticancer Properties.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Enhancing the Effect of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Signaling and Arginine Deprivation in Melanoma.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundArginine-depleting therapy with pegylated arginine deiminase (ADI-PEG20) was reported to have activity in advanced melanoma in early phase I-II trial, and clinical trials are currently underway in other cancers. However, the optimal patient population who benefit from this treatment is unknown.
methodsAdvanced melanoma patients with accessible tumours had biopsy performed before the start of treatment with ADI-PEG20 and at the time of progression or relapse when amenable to determine whether argininosuccinate synthetase (ASS) expression in tumour was predictive of response to ADI-PEG20.
resultsTwenty-seven of thirty-eight patients treated had melanoma tumours assessable for ASS staining before treatment. Clinical benefit rate (CBR) and longer time to progression were associated with negative expression of tumour ASS. Only 1 of 10 patients with ASS-positive tumours (ASS+) had stable disease, whereas 4 of 17 (24%) had partial response and 5 had stable disease, when ASS expression was negative (ASS-), giving CBR rates of 52.9 vs 10%, P=0.041. Two responding patients with negative ASS expression before therapy had rebiopsy after tumour progression and the ASS expression became positive. The survival of ASS- patients receiving at least four doses at 320 IU m(-2) was significantly better than the ASS+ group at 26.5 vs 8.5 months, P=0.024.
conclusionADI-PEG20 is safe and the drug is only efficacious in melanoma patients whose tumour has negative ASS expression. Argininosuccinate synthetase tumour positivity is associated with drug resistance and tumour progression.
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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.