Genetic Landscape and Emerging Therapies in Uveal Melanoma

SIMPLE SUMMARY: Uveal melanoma is the most common primary intraocular malignancy in adults. Unfortunately, metastasis develops in up to 50% of cases and outcomes are poor for these patients. In this review, we discuss our current understanding of the unique genetic landscape of uveal melanoma, and the prognostic and potential therapeutic insight it can provide. By obtaining information on molecular and cytogenetic mutations, patients and their providers can gain important knowledge that may help with surveillance and treatment decisions, including clinical trial enrollment. ABSTRACT: Despite successful treatment of primary uveal melanoma, up to 50% of patients will develop systemic metastasis. Metastatic disease portends a poor outcome, and no adjuvant or metastatic therapy has been FDA approved. The genetic landscape of uveal melanoma is unique, providing prognostic and potentially therapeutic insight. In this review, we discuss our current understanding of the molecular and cytogenetic mutations in uveal melanoma, and the importance of obtaining such information. Most of our knowledge is based on primary uveal melanoma and a better understanding of the mutational landscape in metastatic uveal melanoma is needed. Clinical trials targeting certain mutations such as GNAQ/GNA11, BAP1, and SF3B1 are ongoing and promising. We also discuss the role of liquid biopsies in uveal melanoma in this review.