Pegylated arginine deiminase: a novel anticancer enzyme agent.
Pegylated arginine deiminase (ADI-PEG20) is a novel anticancer enzyme that produces depletion of arginine, which is a nonessential amino acid in humans. Certain tumours, such as malignant melanoma and hepatocellular carcinoma, are auxotrophic for arginine. These tumours that are sensitive to arginine depletion do not express argininosuccinate synthetase, a key enzyme in the synthesis of arginine from citrulline. ADI-PEG20 inhibits human melanomas and hepatocellular carcinomas in vitro and in vivo. Phase I - II trials in patients with melanoma and hepatocellular carcinomas have shown the drug to have antitumour activity and tolerable side effects. Large Phase II trials and randomised, controlled Phase III trials are needed to determine its overall efficacy in the treatment of these malignancies and others.
Feun
Lynn
L
University of Miami, Sylvester Comprehensive Cancer Center, 1475 Northwest 12th Avenue, Miami, FL 33136, USA. lfeun@med.miami.edu
Savaraj
Niramol
N
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001120:Arginine / Q000378:metabolism*; D001124:Argininosuccinate Synthase / Q000172:deficiency / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000201:enzymology; D002956:Citrulline / Q000378:metabolism; D002986:Clinical Trials as Topic; D003907:Dexamethasone / Q000494:pharmacology; D004285:Dogs; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D015507:Drugs, Investigational / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D006867:Hydrolases / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use*; D008113:Liver Neoplasms / Q000188:drug therapy / Q000201:enzymology; D008545:Melanoma / Q000188:drug therapy / Q000201:enzymology; D008546:Melanoma, Experimental / Q000188:drug therapy; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D019535:Mycoplasma hominis / Q000201:enzymology / Q000235:genetics; D009363:Neoplasm Proteins / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D009751:Nutritional Requirements; D011092:Polyethylene Glycols / Q000494:pharmacology / Q000627:therapeutic use*; D011817:Rabbits; D016032:Randomized Controlled Trials as Topic; D011994:Recombinant Proteins / Q000627:therapeutic use; D012878:Skin Neoplasms / Q000188:drug therapy / Q000201:enzymology; D013045:Species Specificity; D016896:Treatment Outcome
D000596:Amino Acids; D000970:Antineoplastic Agents; D015507:Drugs, Investigational; D009363:Neoplasm Proteins; D011994:Recombinant Proteins; D002956:Citrulline; D011092:Polyethylene Glycols; D003907:Dexamethasone; D001120:Arginine; D006867:Hydrolases; C512527:ADI PEG20; D001124:Argininosuccinate Synthase