Feun Lynn, Savaraj Niramol
University of Miami, Sylvester Comprehensive Cancer Center, 1475 Northwest 12th Avenue, Miami, FL 33136, USA.
Expert Opin Investig Drugs. 2006 Jul;15(7):815-22. doi: 10.1517/13543784.15.7.815.
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.
聚乙二醇化精氨酸脱亚氨酶(ADI-PEG20)是一种新型抗癌酶,它能使精氨酸耗竭,而精氨酸在人体中是一种非必需氨基酸。某些肿瘤,如恶性黑色素瘤和肝细胞癌,对精氨酸是营养缺陷型的。这些对精氨酸耗竭敏感的肿瘤不表达精氨琥珀酸合成酶,这是一种由瓜氨酸合成精氨酸的关键酶。ADI-PEG20在体外和体内均能抑制人黑色素瘤和肝细胞癌。针对黑色素瘤和肝细胞癌患者的I-II期试验表明,该药物具有抗肿瘤活性且副作用可耐受。需要进行大规模的II期试验以及随机对照的III期试验来确定其在治疗这些恶性肿瘤及其他肿瘤方面的总体疗效。