Research

Uveal melanoma is a rare ocular melanoma, characterized by driver mutation in G-proteins GNAQ or GNA11. Although primary tumours are readily  treatable, once metastases have been detected survival is between 2-7 months, with no effective treatments available. We are working on identifying new treatments for metastasized UM patients, partly in the context of UMCure2020 (Kseniya). On the one hand by focusing on (combinations of) clinically approved compounds knowing to interfere with oncogenic pathways activated in UM, e.g. PKC inhibitors, mTOR inhibitors.  On the other hand, by investigating the effects of ‘old’ compounds not previously tested in UM, e.g. Aclarubicin.

To identify new druggable targets/pathways in UM we are performing a synthetic lethal CRISPR/Cas9 screen with CRISPR sub-libraries targeting either the kinome or the epigenome.

In addition we are trying to identify differences in phosphorylation status of proteins between primary and metastasis cell lines by mass-spectrometry approach  (in collaboration with Vertegaal lab).

 

Furthermore, we are investigating the oncogenic functions of the p53-regulator Mdmx, which is highly expressed in ~40% of UM. An interesting new link between Mdmx and FOXO family members has recently been elucidated and is being further pursued.

Inhibition of interaction of Mdmx/Mdm2 with p53 (and p73?) is a therapeutic option for UM, which is being investigated.

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