Polaris is collaborating with Dr. Lynn Feun of the University of Miami Sylvester Comprehensive Cancer Center and Dr. Niramol Savaraj of the South Florida Veterans Affairs Foundation on research using ADI-PEG 20 to induce arginine deprivation of melanoma cells. Special interests include characterization of the mechanism of cell death, characterization of the mechanism of drug resistance, and testing of combination treatments of these cells using ADI-PEG 20 together with other drugs.

Dr. Feun is a professor of medicine and co-group leader of the melanoma clinical oncology research program at UM/Sylvester. He is investigating novel therapies, both to increase efficacy and decrease toxicity compared with conventional treatment, and was the principal investigator in a Phase II study of ADI-PEG 20 in patients with metastatic melanoma.

Dr. Savaraj is an attending physician at Miami Veterans Affairs Medical Center and an adjunct professor at the University of Miami. She is currently studying the molecular mechanisms of drug resistance in small cell lung cancer and was the co-investigator in a Phase II study of ADI-PEG 20 in patients with metastatic melanoma.

Arginine deprivation studies are being conducted to help elucidate ADI-PEG 20's mechanism of action and additionally characterize any mechanism by which cells may develop resistance to ADI-PEG 20 treatment. Arginine deprivation via administration of arginine deiminase is known to kill cancer cells in vitro and in vivo. There are many possible mechanisms by which arginine deprivation could result in cell death. These studies are intended to provide insight into the mechanism by which arginine deprivation induces tumor cell death. Combination treatments with other drugs also will be conducted to identify agents that may act synergistically with or potentiate the action of ADI-PEG 20. ADI-PEG 20, both as a single agent and in combination with other drugs, will be tested in cell cultures.