Enzymatic Depletion
Cancer cells, by virtue of their accelerated rate of growth and proliferation, require a readily available supply of amino acids in order to create new proteins. LICR investigators are working with a collaborator to assess whether removing a required amino acid can halt cancer cell growth and proliferation.
Amino acids, the building blocks of proteins, are created by enzymatic reactions within cells. However, some cancers—including melanoma, and liver, pancreatic and prostate cancers—lack the enzyme arginosuccinate synthetase (ASS), which catalyzes the production of the amino acid arginine. To obtain this amino acid and synthesize proteins, cancer cells must scavenge arginine from the blood.
In combination with commercial partner Polaris Pharmaceuticals Inc., LICR is exploring whether depleting arginine from the blood is sufficient to cause cancer cell death by inhibiting protein synthesis. The candidate therapy is an enzyme, arginine deiminase (ADI), which catalyzes the irreversible conversion of arginine into citrulline, another amino acid. The depletion of arginine via ADI does not seem to affect normal cells that still have functional ASS and can thus create more arginine.
LICR is currently sponsoring and conducting a clinical trial assessing ADI safety and tumor response in patients with metastatic melanoma.
