Despite recent development of promising immunotherapeutic and targeted drugs, prognosis in patients with advanced
melanoma remains poor, and a cure for this disease remains elusive in most patients. The success of
melanoma therapy depends on a better understanding of the biology of
melanoma and development of drugs that effectively target the relevant genes or
proteins essential for
tumor cell survival.
Melanoma cells frequently lack
argininosuccinate synthetase, an essential
enzyme for
arginine synthesis, and as a result they become dependent on the availability of exogenous
arginine. Accordingly, a therapeutic approach involving depletion of available
arginine has been shown to be effective in preclinical studies. Early clinical studies have demonstrated sufficient antitumor activity to give rise to cautious optimism. In this article, the rationale for
arginine deprivation
therapy is discussed. Additionally, various strategies for depleting
arginine are discussed and the preclinical and clinical investigations of
arginine deprivation
therapy in
melanoma are reviewed.