Identifying new ways of treating uveal melanoma 

Uveal melanoma (UM) is a rare type of eye cancer caused by malfunctioning pigment cells in the eye called melanocytes. 

It is the most common eye cancer in adults, with the average age of diagnosis being around 60 years old.

In almost all patients, the GNAQ and GNA11 genes are mutated, activating several important signalling pathways that drive the formation of cancerous cells. 

Depending on the size and location of the melanoma, there are several treatment options, including radiotherapy, photodynamic therapy (a treatment that involves light-sensitive medicine and a light source to destroy abnormal cells) and surgery. 

Despite the treatment being successful in the eye itself, up to 50% of patients diagnosed with UM will eventually develop lethal metastatic disease, where the cancerous cells have already spread to other organs via the blood. 

This happens most commonly in the liver. Once spread, these UM cells go through a period of latency and then re-emerge years later, where, at this stage, the cancer is too advanced to be controlled.

There are no effective targeted treatments for metastatic UM, and the mortality rate remains unchanged over the last few decades.

Dr Davide Zecchin, who was recently awarded a career development award, will first be looking into the products of the faulty genes GNAQ and GNA11. 

His previous studies on Sturge-Weber syndrome, a rare neurological and skin condition caused by mutations in the same genes, show that these alterations disrupted vital and previously poorly explored signals inside the cells. 

Deregulation of these pathways may have a major impact on cell proliferation, invasion and survival of uveal melanoma cells.

Davide will investigate if these pathways are similarly activated in UM cells, and he will use different tools to find out the effects of inhibiting these signals.

Using mice, Davide will also be looking to develop a new model of metastatic UM that can be used to explore the mechanisms underpinning UM clinical relapse, which isn’t yet fully understood.

Given the high mortality rates of patients with UM, this research is an important first step to help identify new therapeutic targets and effective treatment plans for UM. 

It will provide background knowledge on new aspects of signalling in UM cells, which could also lead to developing new potential diagnostic or prognostic markers in patients with this condition.

The model of UM metastasis will be key in the future to investigate further mechanisms that allow cancerous cells to survive years before growing, with the aim of developing therapies to intercept or treat early-stage metastatic disease.

Importantly, the knowledge derived from this rare cancer may be extended to other types of tumours metastatic to the liver.