Abstract

A growing understanding of tumor biology has allowed the identification of various cellular characteristics that are more frequently associated with cancer cells than with normal cells. These findings have prompted the development of new therapeutics specifically designed to exploit these differences. In this context, the amino acid depriving enzymes have shown very promising results and proven to be active and very specific against various types of cancers. These therapies involve the depletion of specific amino acids in the bloodstream that cannot be synthesized by tumor cells. This happens because these cells often have a defecting enzymatic armamentarium and therefore rely on external supply for those amino acids. Decreasing the concentration of certain amino acids in blood has thus been shown to impair the development or even destroy tumor cells. Normal cells remain unaltered since they are less demanding and/or can synthesize these compounds in sufficient amounts by other mechanisms.

In this chapter, the structure, function, catalytic mechanism and therapeutic application of some amino acid depriving enzymes will be reviewed. Particular attention will be given to enzymes that have potential or are currently used in the treatment of several types of cancer, namely: (1) l-asparaginase used for the treatment of acute lymphoblastic leukemia; (2) l-arginase and l-arginine deiminase that are used in the therapy of hepatocellular carcinomas and melanomas, two diseases that account annually with approximately 1 million of new cases and for which there is currently no efficacious treatment; and (3) l-Methioninase with potential to be used in the treatment of breast, colon, lung, and renal cancers.