The DOI matches its Crossref record; 86 of the 86 references it cites were found in a registry or an index.
Arginine deprivation and argininosuccinate synthetase expression in the treatment of cancer
Open accessAbstract
Arginine, a semi‐essential amino acid in humans, is critical for the growth of human cancers, particularly those marked by de novo chemoresistance and a poor clinical outcome. In addition to protein synthesis, arginine is involved in diverse aspects of tumour metabolism, including the synthesis of nitric oxide, polyamines, nucleotides, proline and glutamate. Tumoural downregulation of the enzyme argininosuccinate synthetase (ASS1), a recognised rate‐limiting step in arginine synthesis, results in an intrinsic dependence on extracellular arginine due to an inability to synthesise arginine for growth. This dependence on extracellular arginine is known as arginine auxotrophy. Several tumours are arginine auxotrophic, due to variable loss of ASS1, including hepatocellular carcinoma, malignant melanoma, malignant pleural mesothelioma, prostate and renal cancer. Importantly, targeting extracellular arginine for degradation in the absence of ASS1 triggers apoptosis in arginine auxotrophs. Several phase I/II clinical trials of the arginine‐lowering drug, pegylated arginine deiminase, have shown encouraging evidence of clinical benefit and low toxicity in patients with ASS1‐negative tumours. In part, ASS1 loss is due to epigenetic silencing of the ASS1 promoter in various human cancer cell lines and tumours, and it is this silencing that confers arginine auxotrophy. In relapsed ovarian cancer, this is associated with platinum refractoriness. In contrast, several platinum sensitive tumours, including primary ovarian, stomach and colorectal cancer, are characterised by ASS1 overexpression, which is regulated by proinflammatory cytokines. This review examines the prospects for novel approaches in the prevention, diagnosis and treatment of malignant disease based on ASS1 pathophysiology and its rate‐limiting product, arginine.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“For example, some melanoma, lymphoma, glioma, and prostate cancers reduce or lose the expression of the urea cycle enzyme argininosuccinate synthase 1 (ASS1) (Delage et al., 2010).”
From Targeting Metabolism for Cancer Therapy (2017) · cites this paper as Delage et al., 2010
In the citing paper
“Accordingly, the auxotrophy of tumors for arginine is being exploited in the development of anticancer therapies (Delage et al., 2010).”
From The emerging hallmarks of cancer metabolism (2016) · cites this paper as Delage et al., 2010
In the citing paper
“Succination is a hallmark of FH-deficient tumours and an antibody against succinate protein has been proposed as a diagnostic marker for HLRCC89.”
From Coupling Krebs cycle metabolites to signalling in immunity and cancer (2018) · cites this paper as [89]
In the citing paper
“Succination is a hallmark of FH-deficient tumours and an antibody against succinate protein has been proposed as a diagnostic marker for HLRCC89.”
From Coupling Krebs cycle metabolites to signalling in immunity and cancer (2018) · cites this paper as [89]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Arginine metabolism: nitric oxide and beyond
WU, G., & MORRIS, S. M. (1998) · Biochemical Journal · doi:10.1042/bj3360001 · Cited by 2,811
Tumor cell metabolism: cancer's Achilles' heel
Kroemer, G., & Pouyssegur, J. (2008) · Cancer Cell · doi:10.1016/j.ccr.2008.05.005 · Cited by 2,337
Regulation of immune responses by L-arginine metabolism
Bronte, V., & Zanovello, P. (2005) · Nature Reviews Immunology · doi:10.1038/nri1668 · Cited by 1,775
The role of nitric oxide in tumour progression
Fukumura, D., Kashiwagi, S., & Jain, R. K. (2006) · Nature reviews. Cancer · doi:10.1038/nrc1910 · Cited by 1,279
Polyamines and cancer: old molecules, new understanding
Gerner, E. W., & Meyskens, F. L. (2004) · Nature reviews. Cancer · doi:10.1038/nrc1454 · Cited by 1,163
Brick by brick: metabolism and tumor cell growth
DeBerardinis, R. J., Sayed, N., Ditsworth, D., & Thompson, C. B. (2008) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2008.02.003 · Cited by 1,018
Rodrı́guez, P. C., & Ochoa, A. C. (2008) · Immunological Reviews · doi:10.1111/j.1600-065x.2008.00608.x · Cited by 743
Superoxide and peroxynitrite generation from inducible nitric oxide synthase in macrophages
Xia, Y., & Zweier, J. L. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.13.6954 · Cited by 691
Meyskens, F. L., McLaren, C. E., Pelot, D., Fujikawa-Brooks, S., Carpenter, P. M., Hawk, E. T., Kelloff, G. J., Lawson, M. J., Kidao, J., McCracken, J., et al. (2008) · Cancer Prevention Research · doi:10.1158/1940-6207.capr-08-0042 · Cited by 518
Recent advances in arginine metabolism: roles and regulation of the arginases
Morris Jr, S. M. (2009) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2009.00278.x · Cited by 485
Cited by
Sorted by citations
The emerging hallmarks of cancer metabolism
Pavlova, N. N., & Thompson, C. B. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2015.12.006 · Cited by 5,926
Autophagy and autophagy-related pathways in cancer
Debnath, J., Gammoh, N., & Ryan, K. M. (2023) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-023-00585-z · Cited by 1,506
The hallmarks of cancer metabolism: still emerging
Pavlova, N. N., Zhu, J., & Thompson, C. B. (2022) · Cell Metabolism · doi:10.1016/j.cmet.2022.01.007 · Cited by 1,418
mTOR signalling and cellular metabolism are mutual determinants in cancer
Mossmann, D., Park, S., & Hall, M. N. (2018) · Nature reviews. Cancer · doi:10.1038/s41568-018-0074-8 · Cited by 1,088
Targeting Metabolism for Cancer Therapy
Luengo, A., Gui, D. Y., & Vander Heiden, M. G. (2017) · Cell Chemical Biology · doi:10.1016/j.chembiol.2017.08.028 · Cited by 971
Metadata
- Authors
- Delage, B., Fennell, D. A., Nicholson, L., McNeish, I., Lemoine, N. R., Crook, T., & Szlosarek, P. W.
- Affiliations
- Queen Mary University of London (GB)
- Queen's University Belfast (GB)
- King's College London (GB)
- St Bartholomew's Hospital (GB)
- Imperial College London (GB)
- Corresponding author
- Szlosarek, Peter W.
- Venue
- International Journal of Cancer
- Publisher
- Wiley
- Published
- 2010-04-09
- Volume
- 126
- Issue
- 12
- Pages
- 2762-2772
- ISSN
- 0020-7136 (ISSN-L)
- 1097-0215
- OpenAlex
- W2027449497
- Cited by
- 441
- References
- 86
- Citations by year
- 2026: 26 · 2025: 38 · 2024: 28 · 2023: 30 · 2022: 32 · 2021: 51 · 2020: 26 · 2019: 35 · 2018: 32 · 2017: 26 · 2016: 25 · 2015: 20 · 2014: 25 · 2013: 17 · 2012: 12
- FWCI
- 1.61
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- International Journal of Cancer (publishedVersion)
- PubMed (publishedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- Leicester Research Archive (University of Leicester) (submittedVersion)
- Research Portal (Queen's University Belfast) (submittedVersion)
- Funders
- Cancer Research UK (C12522/A8632, 12008)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Bacterial Cancer Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Polyamine Metabolism and Applications
- Keywords
- arginine deprivation, argininosuccinate synthetase, ASS1, arginine auxotrophy, pegylated arginine deiminase, epigenetic silencing, chemoresistance, platinum resistance, ovarian cancer, tumor microenvironment, inflammatory cytokines, hepatocellular carcinoma, melanoma, malignant pleural mesothelioma, prostate cancer, kidney cancer, cancer therapy
- MeSH terms
- Animals, Arginine, Argininosuccinate Synthase, Humans, Neoplasms, Prognosis
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
