Unraveling Uveal Melanoma: Advances in Three-Dimensional Models

Uveal melanoma (UM) is the most common primary intraocular malignancy in adults and remains associated with a high risk of metastatic spread and poor survival once metastasis occurs. Despite advances in the molecular characterization of UM, progress in effective therapeutic strategies has been limited, partly due to the lack of preclinical models that accurately recapitulate the tumor’s complex biology and microenvironment. Traditional two-dimensional (2D) culture systems fail to reflect key features of UM, including cellular heterogeneity, extracellular matrix interactions, and immune modulation. In recent years, three-dimensional (3D) models have emerged as powerful tools to overcome these limitations and to better mimic in vivo tumor architecture and behavior. This review provides a comprehensive overview of the current landscape of 3D UM models, including spheroids and organoids. We discuss their applications in studying UM pathogenesis, tumor–microenvironment interactions, metastatic mechanisms, and therapeutic responses. Advancing 3D modeling approaches holds promise for improving translational research and accelerating the development of effective therapies for uveal melanoma.