“…In vivo, Arginine is synthesized from aspartate or citrulline through argininosuccinate synthetase (ASS1) and argininosuccinate lyase (ASL) (12), which act as key regulators in determining the arginine-dependency of tumor cells. Due to deregulation of ASS1 or ASL (such as loss of ASS1), tumor cells have much a higher demand on extracellular arginine than their normal counter parts, leading to arginine auxotrophy (13)(14)(15)(16). Consequently, depleting arginine through arginase (ARGase, converting arginine into ornithine and urea) or arginine deiminase (ADI, converting arginine into citrulline and NH 3 ) shows great potential in triggering cell death or reducing tumor growth in various cancer types including nonsmall cell lung cancer, glioblastoma, bladder cancer, pancreatic cancer, liver cancer, leukemia and melanoma (11,(16)(17)(18)(19)(20)(21).…”