The latest in vitro models for novel uveal melanoma drug discovery: how effective are they and what needs to be done?

INTRODUCTION: Uveal melanoma (UM) is the most common primary intraocular malignancy in adults, but primary tumor treatment carries a high risk of permanent vision loss and does not adequately prevent metastatic progression. In vitro UM models are needed to accurately represent human disease to support translation of laboratory research to the clinic.

AREAS COVERED: This review covers current and emerging in vitro UM models. A PubMed search used keywords 'uveal melanoma' and 'cell line,' 'spheroid,' 'organoid,' 'culture,' or 'in vitro' to identify cell lines, three-dimensional (3D) cultures (spheroids and organoids), and co-culture systems. Model successes and shortcomings are described, considering features that make models more or less representative of in vivo human UM. Insights are provided for consideration when selecting UM models for novel drug discovery.

EXPERT OPINION: While traditional cell lines have provided an important foundation for UM research, emerging spheroid and patient-derived organoid models may more accurately represent in vivo tumor behavior and the tumor microenvironment. Pairing these 3D models with co-culture techniques could dramatically improve the representativeness of UM models. Researchers should consider testing promising therapeutics on a panel of models representing different UM subtypes, with particular attention to high-risk UM, such as those with BAP1 loss.