Metastatic Uveal Melanoma—A Review of Current Therapies and Future Directions

Abstract

The most common type of ocular melanoma is uveal melanoma, which includes melanomas that originate from the choroid, iris, or ciliary body. Although the survival rate for all cases of uveal melanoma is high, once metastatic disease occurs the survival rate drops dramatically. Currently no standard of care exists to guide management in metastatic uveal melanoma. The molecular biology in uveal melanoma is distinct from cutaneous melanoma. In most cases of uveal melanoma, the mitogen activated protein kinase (MAPK) pathway is activated through mutations in either GNAQ or GNA11. In uveal melanoma the most common site of metastatic disease is the liver, and a number of hepatic-directed therapies are available including surgery, radiofrequency ablation, and embolization. Conventional systemic chemotherapy has shown poor response rates in uveal melanoma. An increased understanding of the molecular genetics and intracellular signaling of uveal melanoma has led to the development of immunotherapy and targeted systemic therapies. This review will discuss the options for metastatic uveal melanoma including hepatic-directed therapies, systemic therapies, and future directions.