Uveal melanoma (UM) is a type of aggressive eye cancer that often spreads to the liver and has a poor prognosis. We don’t fully understand how UM spreads, which makes it difficult to develop targeted treatments. In this study, we created a new model of UM by injecting human cancer cells into the eyes of mice. This model consistently led to large liver metastasis, whereas other organs were not as strongly affected, mimicking how UM behaves in humans.

Our goal is to figure out the main factors that drive UM to spread and specifically target the liver. Firstly, we think a protein called hepatocyte growth factor (HGF) and its receptor c-Met might be important for the cancer cells to colonize the liver. We will use a gene editing technique called CRISPR to turn off c-Met and see if it affects the cancer’s ability to spread to the liver. Secondly, we believe that a pathway called NRF2, which is activated by a protein called MITF, is crucial for UM metastasis. We will use genetic methods and a new drug called DF-52A to investigate the role of NRF2 in the cancer’s ability to spread. We will monitor tumor growth and metastasis using imaging techniques and flow cytometry.

If successful, these studies could provide evidence for targeting c-Met and NRF2 as potential therapies to prevent UM from spreading. Additionally, our experimental model allows us to identify other pathways involved in the spread of UM. The findings from this research will improve our understanding of how UM spreads and help develop better treatments.