In 2002, Ensor et al. (2002) published the first study linking ASS1 expression to the efficacy of ADI-PEG20 in melanoma and hepatocellular carcinoma cell lines, which showed remarkable results in early clinical trials and was granted orphan drug designation by the FDA for the treatment of malignant melanoma and hepatocellular carcinoma (HCC). Here, ASS1 is linked to hepatocellular carcinoma.