ArticleCell death & disease2016
A metabolic synthetic lethal strategy with arginine deprivation and chloroquine leads to cell death in ASS1-deficient sarcomas.
Article in Cell death & disease, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 1 of them a synthesis that pooled it.
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Who cites it
58 citing papers in PubMed, 1 synthesis or guideline pooled it, 99 citations in OpenAlex.
- Perspective: Do Fasting, Caloric Restriction, and Diets Increase Sensitivity to Radiotherapy? A Literature Review.Advances in nutrition (Bethesda, Md.) · 2020Pooled it
- 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
- Article
- The role of L-Arginine metabolism in the hallmarks of cancer as an emerging pathway to drug design.Frontiers in pharmacology · 2026Review
- New Approaches to Investigate Novel Agents in Ewing Sarcoma: A Report From the Children's Oncology Group Bone Tumor Committee.Pediatric blood & cancer · 2025Review
- Extract ofToxins · 2025Article
- Arginine depletion potentiates standard-of-care chemo-immunotherapy in preclinical models of high-risk neuroblastoma.Journal of experimental & clinical cancer research : CR · 2025Article
- Low-Dose Salinomycin Alters Mitochondrial Function and Reprograms Global Metabolism in Burkitt Lymphoma.International journal of molecular sciences · 2025Article
- BCL-XL Protects ASS1-Deficient Cancers from Arginine Starvation-Induced Apoptosis.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Advances in prognostic models for osteosarcoma risk.Heliyon · 2024Review
- Autophagy: a necessary evil in cancer and inflammation.3 Biotech · 2024Review
- FOXO3a-regulated arginine metabolic plasticity adaptively promotes esophageal cancer proliferation and metastasis.Oncogene · 2024Article
- The regulation of amino acid metabolism in tumor cell death: from the perspective of physiological functions.Apoptosis : an international journal on programmed cell death · 2023Review
- Discovery and Targeting of a Noncanonical Mechanism of Sarcoma Resistance to ADI-PEG20 Mediated by the Microenvironment.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- The proteomic landscape of soft tissue sarcomas.Nature communications · 2023Article
- Unlocking the Potential of Arginine Deprivation Therapy: Recent Breakthroughs and Promising Future for Cancer Treatment.International journal of molecular sciences · 2023Review
- Relapsed Synovial Sarcoma: Treatment Options.Current treatment options in oncology · 2023Review
- Bench-to-Bedside Studies of Arginine Deprivation in Cancer.Molecules (Basel, Switzerland) · 2023Review
- Functional identification of two novel variants and a hypomorphic variant inFrontiers in genetics · 2023Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
Sarcomas comprise a large heterogeneous group of mesenchymal cancers with limited therapeutic options. When treated with standard cytotoxic chemotherapies, many sarcomas fail to respond completely and rapidly become treatment resistant. A major problem in the investigation and treatment of sarcomas is the fact that no single gene mutation or alteration has been identified among the diverse histologic subtypes. We searched for therapeutically druggable targets that are common to a wide range of histologies and hence could provide alternatives to the conventional chemotherapy. Seven hundred samples comprising 45 separate histologies were examined. We found that almost 90% were arginine auxotrophs, as the expression of argininosuccinate synthetase 1 was lost or significantly reduced. Arginine auxotrophy confers sensitivity to arginine deprivation, leading temporarily to starvation and ultimately to cell survival or death under different circumstances. We showed that, in sarcoma, arginine deprivation therapy with pegylated arginine deiminase (ADI-PEG20) maintains a prolonged state of arginine starvation without causing cell death. However, when starvation was simultaneously prolonged by ADI-PEG20 while inhibited by the clinically available drug chloroquine, sarcoma cells died via necroptosis and apoptosis. These results have revealed a novel metabolic vulnerability in sarcomas and provided the basis for a well-tolerated alternative treatment strategy, potentially applicable to up to 90% of the tumors, regardless of histology.
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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.