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2023 Ocular Melanoma Update

Posted by Ilena Di Toro | Posted on May 23, 2023

Ocular melanoma, despite its name is not caused by exposure to the sun. This type of cancer is found in Caucasians between the ages of 30 and 50 and occurs in 1 out of 2,500 people. As you can guess, it can cause vision loss or blindness and can spread to the brain and liver. Treatments for this disease include radiation and enucleation or removal of the eye. In two percent of the cases, ocular melanoma is inherited from the parent and is known as BAP-1 cancer predisposition syndrome.

In spite of it being a rare cancer, there have been groups of people with this cancer in North Carolina and Alabama. The people in the North Carolina group live in Huntersville, near Charlotte, North Carolina. Most live or lived near the town’s high school. The soil around the high school was tested in 2019 and no chemical contamination linked to ocular melanoma was found. All the people in the Alabama group went to Auburn University, all majored in education and two belonged to the same sorority.

In addition to the groups in North Carolina and Alabama, Ireland has one of the highest rates in the world of this disease. Research in Ireland has shown that a drug and biomarker may be able to help in the management of this disease. Led by Professor Breandán Kennedy at the University College Dublin School of Biomolecular & Biomedical Science, scientists first focused on molecules, known as cysteinyl leukotriene, to see if they are biomarkers and if they can be used as drug targets. Cysteinyl leukotriene is involved in inflammation, plays a role in asthma and has been shown to involve in central nervous system diseases and cancer.

Kennedy’s team used patient samples and experimental models to investigate whether the molecules are linked to patient survival and to learn more about the effects of the drug 1,4-dihydroxy quininib. First, the data showed that the higher cysteinyl leukotriene receptor levels in the tumor was an indication of a poor prognosis. Second, 1,4-dihydroxy quininib affected the molecular characteristics that allowed the cancer to grow and spread. Third, they found a biomarker that seems to predict which patients will not develop metastatic disease.

On the treatment front, an immunotherapy drug tebentafusp has helped patients to live longer than patients who received current treatments. Tebentafusp, is a treatment known as a bispecific fusion protein and it works by helping immune cells get close enough to the cancer cells to attack them. In a clinical trial, 378 patients were randomly assigned to receive either tebentafusp or one of the three established therapies that their doctor can select. The options in the comparison or control group included two immune checkpoint inhibitors and a chemotherapy drug.

The survival rate of the patients receiving tebentafusp was 21.7 months, whereas the survival rate for the control group was 16 months. While immune checkpoint inhibitors can improve the survival of those with skin melanomas, it hasn’t been as effective in those with ocular melanoma. Researches wanted to see if a bispecific fusion protein could overcome that resistance. Tebentafusp does that by attaching itself to one molecule on melanoma cells and another to T cells, a type of immune cell. The drug brings the T cells close enough to the melanoma cells in order to kill it. What makes tebentafusp so effective is that it recognizes part of the gp100 protein, something that is abundant in melanoma cells. Since tebentafusp also binds to T cells, it activates the T cells to attack the gp100-expressing cells.

Another promising treatment for ocular melanoma involves proton therapy. While traditional radiation delivers X-Rays to a tumor, this kind of radiation can go beyond the tumor and damage healthy tissue. Proton therapy delivers radiation via a beam through the white of the eye, which is resistant to radiation, and it stops at the tumor. No radiation makes it way to the brain. Of course, it is important to catch the melanoma early, since proton therapy, when utilized at ocular melanoma’s early stage, has a cure rate of almost 95 percent. Not only does this therapy save a person’s life, the eye and vision are preserved, as well.

The search for both treatments and, in the case of the Alabama and North Carolina ocular melanoma groups, the cause is ongoing.


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