title: Treatment of Uveal Melanoma.
abstract: Uveal melanoma (UM) comprises approximately 5 % of all melanoma diagnoses in the USA each year. Approximately half of patients with UM eventually develop metastases, most commonly involving the liver. Historically, prognosis for these patients has been poor, with death occurring 6-12 months from the time of metastases. Multiple trials of cytotoxic treatments largely extrapolated from cutaneous melanoma have been ineffective in metastatic UM. Trials of regional hepatic-directed therapy have led to high response rates, but these have yet to be translated into a survival benefit. Recently, it was discovered that the majority of UMs harbor activating mutations in genes encoding one of two G-alpha protein subunits, GNAQ and GNA11. This knowledge has led to the rational development of clinical trials specifically for UM utilizing targeted inhibitors of the activated signaling pathways such as mitogen-activated protein kinase, Akt, and protein kinase C. A recent trial of the oral MEK inhibitor selumetinib was the first to show clinical benefit for any systemic therapy in a randomized fashion. This increasing understanding of the biology of UM offers hope that novel treatments will continue to benefit patients with metastatic disease.
authors.affiliation: Melanoma and Immunotherapeutics Service, Memorial Sloan Kettering Cancer Center, 300 East 66th Street, New York, NY, 10065, USA. shoushta@mskcc.org.
authors.forename: Alexander N
authors.initials: AN
authors.lastname: Shoushtari
authors.affiliation: Melanoma and Experimental Therapeutics Services, Columbia University Medical Center, 161 Fort Washington Avenue, New York, NY, 10032, USA. rdc2150@cumc.columbia.edu.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Carvajal
mesh_terms: D006801:Humans; D007167:Immunotherapy; D008545:Melanoma / Q000473:pathology / Q000628:therapy*; D058990:Molecular Targeted Therapy; D009367:Neoplasm Staging; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D014604:Uveal Neoplasms / Q000473:pathology / Q000628:therapy*
chemical_list: D047428:Protein Kinase Inhibitors
keywords: MAP Kinase; MEK; Protein Kinase C; Selumetinib; Uveal melanoma