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Many medical centers around the world are doing research on the causes and treatment of eye cancers. These are challenging diseases to study because they are not common. But each year scientists find out more about what causes them and how to improve treatment.

Genetics

Learning more about the gene changes that make eye cancer cells different from normal cells will likely play an important role in treating eye melanomas in the future.

Using genes to help find people at higher risk

As we learn about the gene changes in these cancers, we may be able to develop tests to identify people who are more likely to get them and then carefully screen those people.

For example, in recent years, researchers have found that some families have a change (mutation) in the BAP1 gene that makes them more likely to develop melanoma of the eye. While this gene change affects only a small portion of people with eye melanoma, researchers might be able to study it to learn more about how eye melanomas develop.

Using genes to help predict prognosis (outlook)

The genetic changes in tumors may also help predict the likelihood of them spreading. For example, in uveal melanoma, certain genetic changes, such as the loss of one copy of chromosome 3, have been linked to an increased risk of cancer spread.

Recently, researchers have found that patterns of gene expression in tumor cells appear to be an even better way to tell if an eye melanoma is likely to spread. Based on these gene patterns, a little more than half of eye melanomas are shown to be “Class 1” tumors. These cancers have a low risk of spreading. The remaining eye melanomas fall into the “Class 2” category, which have a very high risk of spreading.

Some doctors now offer a test (DecisionDx-UM) for these gene changes, and some patients may want to have them to learn if their cancer is likely to spread. If a patient is found to be at high risk, the doctor might follow them more closely to try to detect cancer spread as early as possible. But other doctors are not as keen on using the test at this time, because we don’t yet have proven ways to prevent the cancer spread or alter the outcome in people who are in the high risk group.

Using genes to help find new treatments

Identifying gene changes in eye cancer cells might also provide specific targets for newer drugs. For example, most eye melanomas have changes in either of 2 related genes, GNAQ or GNA11. The proteins made by these genes are part of the MAPK signaling pathway inside cells that helps them grow. It’s not yet clear if drugs will be able to target these proteins directly, but drugs that target other proteins in the MAPK pathway are now being studied for use against eye melanomas, and some have shown early promising results. (See "Targeted therapy" below.)

New tests for eye cancer

A new type of biopsy called a liquid biopsy is being looked at more often. Instead of having to make a cut or put a needle into the eye, melanoma tumor cells can be collected from a blood sample. These cancer cells can then be tested for certain traits, including genetic changes, that can help predict how likely the cancer is to spread or come back after treatment. Liquid biopsies might help diagnose tumor spread earlier, or help the doctors know if treatment is working. This could be very helpful in people who did not have a biopsy of the tumor and want to preserve their vision. However, the equipment needed for this test is not readily available, so this type of biopsy is not done routinely and is mainly done as part of a clinical trial.

Advances in treatment

Immunotherapy

Immunotherapies are treatments that boost the body’s immune system to help it attack the cancer. Cytokines, monoclonal antibodies, cancer vaccines, and other immunotherapies are among the most promising approaches for treating melanoma. Although most clinical trials of these treatments focus on people with melanomas of the skin, results of these studies might help treat people with eye melanomas as well. For example:

• Drugs known as immune checkpoint inhibitors, which help boost the body’s immune response, have been shown to be helpful in many people with skin melanomas. They might also be an option in some people with eye melanomas.
• Bispecific T cell engagers (BiTEs) are drugs that help bring immune cells called T cells together with melanoma cells, which can help boost the body’s immune response. One of these drugs, tebentafusp, is now an option to treat some people with advanced eye melanomas.

Other new immunotherapy drugs are now being studied as well.

Targeted therapy drugs

As researchers have learned more about some of the changes in cells that cause them to become cancer, they have developed drugs that target these changes. These new targeted drugs work differently from standard chemo drugs. They might work in some cases when chemo drugs don’t, and they tend to have different side effects.

Most eye melanomas have changes in the GNAQ or GNA11 genes. Proteins made by these genes are part of the MAPK gene signaling pathway that helps cells grow. Selumetinib is a drug that targets the MEK protein, which is also part of the MAPK pathway. Selumetinib has been shown to slow the growth of advanced eye melanomas in one clinical trial, but other studies have had disappointing results. The role of selumetinib in treating eye melanoma is not clear and for now, this drug is only available through clinical trials.

Some newer drugs, such as vemurafenib, dabrafenib, and trametinib, target cells with a mutation in the BRAF gene. This mutation is found in about half of patients with skin melanoma, but only in about 5% of patients with eye melanoma. Still, these or similar drugs might help people whose cancer cells have these mutations.

IMCgp100 is a new drug that attaches to two proteins at the same time to kill cancer cells. It shows promising results in people with advanced uveal melanoma. More research is being done.

Many targeted drugs are already used to treat other types of cancer. Some of them are now being studied for use against melanoma of the eye as well, including sunitinib, sorafenib, vorinostat , and everolimus.

To learn more about immunotherapy and targeted drugs now being used to treat eye melanoma, see Targeted Drugs and Immunotherapy for Eye Cancer.