Polaris is collaborating with Dr. Peter Szlosarek of the Institute of Cancer, Barts and London School of Medicine and Dentistry, on aberrant expression of argininosuccinate synthetase (ASS) in certain cancers such as mesothelioma. 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. Szlosarek is a principal investigator at the Centre for Molecular Oncology and Imaging in the Cancer Institute at Barts and London, Queen Mary's School of Medicine and Dentistry, London. He received his medical degree from King's College London and his Ph.D. from the Institute of Cancer. His clinical and research interests are focused on the biological treatment of mesothelioma and melanoma.
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. Dissection of the arginine/ASS pathway may yield novel insights into the prevention, diagnosis and therapy of malignant disease.
Mesothelioma is a form of cancer that originates in the membrane that covers and protects most of the internal organs of the body. Standard treatment options include surgery, radiation therapy, and chemotherapy; however, more treatment options are needed as mesothelioma is hard to control. Studies are underway to determine if this ASS- deficient cancer would be a good candidate for treatment with ADI-PEG 20.