Biomarkers in uveal melanoma progression: Insights and discoveries

Uveal melanoma (UM) is a rare but aggressive eye cancer that frequently spreads to other organs. This thesis uncovers key insights into the biology of UM, including the role of RNA splicing errors, particularly mutations in the SF3B1 gene, which influence disease progression and patient outcomes. Differences in gene activity were linked to varying risks of metastasis, offering potential predictive markers.

The work also tested the experimental drug E7107, which blocks abnormal splicing and was shown to induce cancer cell death in SF3B1-mutant tumors. This suggests splicing inhibitors may be promising treatment options, especially in combination with other therapies. In addition, genetic markers such as chromosome 8q changes and genes like FOXD1 and RBFOX2 were identified as drivers of aggressive disease and poor survival.

Finally, progress was made in developing advanced laboratory models of UM using gene-editing technologies. These models will be vital for understanding tumor evolution and testing new therapies. Altogether, the findings of this thesis contribute valuable knowledge that brings research closer to more effective treatments for UM patients.