{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:11:15Z","timestamp":1792789875729,"version":"4.5.0"},"reference-count":91,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,2,24]],"date-time":"2023-02-24T00:00:00Z","timestamp":1677196800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Polaris Pharmaceuticals, Inc."},{"name":"charitable donations to Professor Szlosarek\u2019s group"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Arginine is a semi-essential amino acid which becomes wholly essential in many cancers commonly due to the functional loss of Argininosuccinate Synthetase 1 (ASS1). As arginine is vital for a plethora of cellular processes, its deprivation provides a rationale strategy for combatting arginine-dependent cancers. Here we have focused on pegylated arginine deiminase (ADI-PEG20, pegargiminase)\u2013mediated arginine deprivation therapy from preclinical through to clinical investigation, from monotherapy to combinations with other anticancer therapeutics. The translation of ADI-PEG20 from the first in vitro studies to the first positive phase 3 trial of arginine depletion in cancer is highlighted. Finally, this review discusses how the identification of biomarkers that may denote enhanced sensitivity to ADI-PEG20 beyond ASS1 may be realized in future clinical practice, thus personalising arginine deprivation therapy for patients with cancer.<\/jats:p>","DOI":"10.3390\/molecules28052150","type":"journal-article","created":{"date-parts":[[2023,2,27]],"date-time":"2023-02-27T02:10:46Z","timestamp":1677463846000},"page":"2150","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Bench-to-Bedside Studies of Arginine Deprivation in Cancer"],"prefix":"10.3390","volume":"28","author":[{"given":"George C.","family":"Field","sequence":"first","affiliation":[{"name":"Centre for Cancer Biomarkers and Biotherapeutics, Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iuliia","family":"Pavlyk","sequence":"additional","affiliation":[{"name":"Centre for Cancer Biomarkers and Biotherapeutics, Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter W.","family":"Szlosarek","sequence":"additional","affiliation":[{"name":"Centre for Cancer Biomarkers and Biotherapeutics, Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK"},{"name":"Department of Medical Oncology, St. Bartholomew\u2019s Hospital, Barts Health NHS Trust, West Smithfield, London EC1A 7BE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4957","DOI":"10.1038\/onc.2016.37","article-title":"Arginine dependence of tumor cells: Targeting a chink in cancer\u2019s armor","volume":"35","author":"Patil","year":"2016","journal-title":"Oncogene"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/bj3360001","article-title":"Arginine metabolism: Nitric oxide and beyond","volume":"336","author":"Wu","year":"1998","journal-title":"Biochem. 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