Consequently, these cells have a particular reliance on the import of a given amino acid(s) from the extracellular serum pool. Extensive in vitro, in vivo, and clinical evaluations conducted over the past sixty years have established that this type of metabolic liability can be exploited through enzyme-mediated systemic depletion of a circulating “tumor-essential” amino acid, resulting in the selective starvation and death of targeted auxotrophic malignant cells with minimal effect on normal cells