What’s New in Eye Cancer Research?

Many medical centers around the world are doing research on the causes, testing, and treatment of eye cancer, especially melanoma of the eye (also known as ocular melanoma or intraocular melanoma).

Eye cancers are challenging to study because they are not common. But each year scientists find out more about what causes them and how to improve treatment.

Research into genetics

Learning more about the gene changes (mutations) that make eye melanoma cells different from normal cells could help in finding and treating these cancers in the future.

Using gene changes to find people at higher risk

As researchers learn more about the gene changes in eye cancer cells, they may be able to test people to identify who might be more likely to get eye cancer and  carefully screen them.

For example, some families have a change in the BAP1 gene that increases their risk for eye melanoma. This mutation affects only a small number of people, but studying it could help researchers learn more about how these cancers develop.

Using gene changes to predict prognosis (outlook)

Certain gene or chromosome changes in eye cancer cells may help predict the likelihood of the cancer spreading.

Gene expression profiling, which looks at patterns of gene expression in tumor cells, can often help tell how likely it is that an eye melanoma will spread.

• Class 1 tumors (a little more than half of eye melanomas) have a lower risk of spreading.
• Class 2 tumors have a higher risk.

Some doctors offer a test called DecisionDx-UM for these gene changes. People found to be at high risk may be monitored more closely to find cancer spread as early as possible.

One challenge is that we don’t yet have proven ways to prevent the cancer spread. But some studies are looking at whether giving additional (adjuvant) treatment after radiation or surgery might lower the risk of the cancer coming back, especially in people who are at high risk. If the cancer does spread, finding it early with more frequent monitoring might allow for more treatment options.

Using gene changes to find new treatments

Finding gene changes in eye cancer cells might help researchers develop targeted treatments. Most eye melanomas have changes in the GNAQ or GNA11 gene. These genes make proteins that 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. (See "Targeted therapy" below.)

New tests for eye cancer

A newer type of biopsy called a liquid biopsy is being studied as a way collect cancer cells for testing without having to make a cut or put a needle into the eye.

Instead, a blood sample is taken. If melanoma cells are present, they can be tested for genetic changes that may help predict how likely the cancer is to spread or come back after treatment.

A drawback of this test is that not all eye tumors shed cancer cells into the blood, so this type of test might not be helpful for everyone.

Liquid biopsies are not yet done routinely for eye melanoma. It is more likely to be done as part of a clinical trial.

Advances in eye cancer treatment

Immunotherapy

Immunotherapies are treatments that boost the body’s immune system to help it attack the cancer. These medicines are among the most promising approaches for treating more advanced eye melanomas. For example:

• Immune checkpoint inhibitors, which help boost the body’s immune response, are often helpful in treating skin melanomas. They might also be an option for some people with eye melanomas.
• T cell engagers (TCEs) are drugs that help bring immune cells called T cells together with melanoma cells, which can help boost the body’s immune response against the cancer. One of these drugs, tebentafusp, is now an option to treat some advanced eye melanomas. It is also being studied in earlier stage melanomas to see if it can help lower the risk of the cancer coming back after radiation or surgery.
• Tumor-infiltrating lymphocytes (TILs) are immune system cells that have entered (infiltrated) a tumor to attack the cancer cells. Once a tumor is removed with surgery, the TILs can be separated out and multiplied in the lab, then given back to the person through an IV infusion. Treatments using these cells help shrink some skin melanomas, and they are now being studied for eye melanomas, too.

Other new immunotherapy drugs are also being studied.

Targeted therapy drugs

As researchers have learned more about the gene and protein changes in cells that cause them to become cancer cells, they have developed drugs that target some of these changes. These 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.

Drugs that target cancer cells with BRAF gene changes are now an important part of treatment for many people with advanced skin melanomas. Unfortunately, most eye melanomas don’t share the same gene changes commonly found in skin melanoma cells, so these drugs aren’t as likely to be helpful.

However, drugs targeting other gene or protein changes that are more common in eye melanoma cells are now being studied in clinical trials. Examples include:

• DYP688, a drug that targets cells with GNAQ or GNA11 gene mutations, which are common in eye melanomas
• Darovasertib, a drug that targets protein kinase C (PKC)

Many other 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 olaparib and lenvatinib.

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