Arginine deprivation therapy for malignant melanoma

Jung-Ki Yoon,1,2 Arthur E Frankel,3 Lynn G Feun,4 Suhendan Ekmekcioglu,1 Kevin B Kim11Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; 2Hwasung Public Health Center, Hwasung, South Korea, 3Scott and White Cancer Research Institute, Temple, TX, USA; 4Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USAAbstract: 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.Keywords: arginine deprivation, argininosuccinate synthetase, melanoma