Molecular Insights and Emerging Strategies for Treatment of Metastatic Uveal Melanoma

SIMPLE SUMMARY: Around 50% of patients with uveal melanoma (UM) still develop metastatic disease. Despite recent advances in the diagnosis and prognosis of UM, improvements in overall survival have not been achieved. At present, there is no available standard of care for adjuvant and metastatic settings. The aim of our review article was to discuss the latest advances in understanding the molecular mechanisms underlying uveal melanoma and novel treatment options for metastatic disease. We provided a detailed analysis of the most recently published works in the Literature along with a number of ongoing clinical trials for adjuvant and metastatic treatment of uveal melanoma. New insights into the pathogenesis of UM and promising results from the study of innovative tailored therapies could offer viable opportunities for translating in clinical practice. ABSTRACT: Uveal melanoma (UM) is the most common intraocular cancer. In recent decades, major advances have been achieved in the diagnosis and prognosis of UM allowing for tailored treatments. However, nearly 50% of patients still develop metastatic disease with survival rates of less than 1 year. There is currently no standard of adjuvant and metastatic treatment in UM, and available therapies are ineffective resulting from cutaneous melanoma protocols. Advances and novel treatment options including liver-directed therapies, immunotherapy, and targeted-therapy have been investigated in UM-dedicated clinical trials on single compounds or combinational therapies, with promising results. Therapies aimed at prolonging or targeting metastatic tumor dormancy provided encouraging results in other cancers, and need to be explored in UM. In this review, the latest progress in the diagnosis, prognosis, and treatment of UM in adjuvant and metastatic settings are discussed. In addition, novel insights into tumor genetics, biology and immunology, and the mechanisms underlying metastatic dormancy are discussed. As evident from the numerous studies discussed in this review, the increasing knowledge of this disease and the promising results from testing of novel individualized therapies could offer future perspectives for translating in clinical use.