Arginine deprivation with pegylated arginine deiminase may improve PFS and prolong life expectancy in patients with argininosuccinate synthetase 1–deficient malignant pleural mesothelioma, according to the results of a randomized phase 2 trial.
The incidence of malignant pleural mesothelioma has risen in the United States and in Europe. The disease has a median survival from diagnosis of less than 1 year, and few validated treatment options exist.
“To our knowledge, we were the first to show that an exogenous supply of the amino acid arginine is critical for the survival of mesothelioma cell lines displaying loss of the urea cycle and arginine biosynthetic enzyme argininosuccinate synthetase 1 (ASS1),” Peter W. Szlosarek, MD, PhD, clinical senior lecturer at Barts Cancer Institute and Barts and The London School of Medicine and Dentistry, in London, and colleagues wrote. “Various ASS1–negative tumors have been shown to be sensitive to arginine depleters, mycoplasmal-derived pegylated arginine deiminase (ADI-PEG20, Polaris Group) and recombination human arginases, in preclinical studies.”
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