title: The role of arginine and the modified arginine deiminase enzyme ADI-PEG 20 in cancer therapy with special emphasis on Phase I/II clinical trials.
abstract: BACKGROUND
  The metabolic differences between normal, healthy cells and neoplastic cells have been exploited by anticancer therapies targeting metabolic pathways. Various studies of malignant processes have demonstrated disturbances in both arginine synthesis and metabolism that enhance or inhibit tumor cell growth. Consequently, there has been an increased interest in the arginine-depleting enzyme arginine deiminase (ADI) as a potential antineoplastic therapy.
  
  
  METHODS
  This review summarizes the literature on the potential anti-cancer therapeutics arginine and ADI, an arginine-catabolizing enzyme. The authors searched the MEDLINE database PubMed using the key words: 'arginine, 'ADI', 'arginine in cancer' and 'ADI and cancer'. The authors evaluate prospective randomized studies on cancer patients between 2004 and 2013 as well as ongoing research found through the US National Institutes of Health trial database.
  
  
  CONCLUSIONS
  The results of current studies are promising but do not give unequivocal answers and so it is impossible to recommend arginine or its enzyme ADI as a therapeutic. In the opinion of the authors, further identification of arginine-dependent malignant tumors and their metabolism should be investigated. Furthermore, the use of these chemicals, in combination with other chemotherapeutics drugs, should be investigated and indeed may improve the success of arginine-depleting enzymes such as pegylated ADI (ADI-PEG20).
authors: Medical University of Gdansk, Department of Pediatrics, Hematology and Oncology , 7 Debinki Street, 80-211 Gdansk , Poland +48 58 3492880 ; +48 58 349 2847 ; anna.synakiewicz@gmail.com.
authors: Anna
authors: A
authors: Synakiewicz
authors: Teresa
authors: T
authors: Stachowicz-Stencel
authors: Elzbieta
authors: E
authors: Adamkiewicz-Drozynska
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001120:Arginine / Q000378:metabolism / Q000627:therapeutic use; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D006801:Humans; D006867:Hydrolases / Q000494:pharmacology / Q000627:therapeutic use*; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011092:Polyethylene Glycols / Q000494:pharmacology / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic
chemical_list: D000970:Antineoplastic Agents; D011092:Polyethylene Glycols; D001120:Arginine; D006867:Hydrolases; C512527:ADI PEG20
keywords: arginine; arginine deiminase; cancer; clinical trials; targeted anticancer therapy