Treatment of uveal melanoma: where are we now?

Abstract

Uveal melanoma, a rare subset of melanoma, is the most common primary intraocular malignancy in adults. Despite effective primary therapy, nearly 50% of patients will develop metastatic disease. Outcomes for those with metastatic disease remain dismal due to a lack of effective therapies. The unique biology and immunology of uveal melanoma necessitates the development of dedicated management and treatment approaches. Ongoing efforts seek to optimize the efficacy of targeted therapy and immunotherapy in both the adjuvant and metastatic setting. This review provides a comprehensive, updated overview of disease biology and risk stratification, the management of primary disease, options for adjuvant therapy, and the current status of treatment strategies for metastatic disease.

Keywords: adjuvant therapy; immunotherapy; liver-directed therapy; targeted therapy; uveal melanoma.

Figure 1.

G-alpha signaling pathway in uveal melanoma (adapted from Patel M et al. Clin Cancer Res 2011; 17(8): 2087–2100). G-protein coupled receptors (GPCR) signal through the heterotrimeric proteins, Gα and Gβγ. Mutations in GNAQ or GNA11 lead to constitutive activation of Gα and downstream stimulation of the mitogen-activated protein kinase (MAPK) pathway via phospholipase C (PLCβ) and protein kinase C (PKC). The phosphotidylinositol-3 kinase (PI3K)/Akt/mTOR and the Yes-activated protein (YAP) pathways are also activated. All three signaling pathways contribute to tumor growth and proliferation. Targeted therapy against various downstream effectors have had limited clinical efficacy. ORR - overall response rate; PFS - progression-free survival.