Polaris is collaborating with Dr. Pei-Jer Chen of the National Taiwan University Hospital, Hepatitis Research Center to determine argininosuccinate synthetase (ASS) gene expression levels in cancer patients. ASS is one of two enzymes required to convert citrulline to arginine. Patients with tumor types identified as ASS-deficient should be the most likely to respond to arginine deprivation therapy.
Dr. Chen's lab uses immunohistochemistry and quantitative RT-PCR to identify tumor types that may be auxotrophic for arginine. Patients diagnosed with these tumor types may benefit from treatment with ADI-PEG 20.
Argininosuccinate synthetase is one of the enzymes comprising the urea cycle. It catalyzes the union of citrulline and aspartate to form argininosuccinate, the first of two steps that allows cells to synthesize arginine from citrulline. Studies have shown that some human tumor cell lines are deficient in ASS, making them auxotrophic for arginine and thus susceptible to arginine deprivation therapy.