What’s new in eye cancer research and treatment?
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.
Learning more about the gene changes involved in these cancers will likely play an important role in treating intraocular melanomas, intraocular lymphomas, and other eye cancers 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 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)
Genetic profiles of tumors may also help predict the likelihood of the tumor 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 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 what is likely to happen in their case. 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 found to be in the high risk group.
Using genes to help find new treatments
Identifying gene changes might also provide specific targets for which newer drugs may work. For example, most eye melanomas have been found to have changes in either of 2 related genes, GNAQ or GNA11. 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 gene changes directly, but drugs that target other genes in the MAPK pathway are now being studied for use against eye melanomas, and some have shown early promising results (see targeted therapy below).
Immunotherapies are treatments that boost the body’s own immune system to try to get it to attack the cancer. Cytokines, monoclonal antibodies, vaccines, and other immunotherapies are among the most promising approaches for treating melanoma and lymphoma. Although most clinical trials of these treatments include people with melanomas of the skin and lymphomas that begin in lymph nodes, results of these studies may help treat people with intraocular melanoma and lymphoma as well.
One example is ipilimumab (Yervoy), a type of drug called a monoclonal antibody that boosts the overall activity of the immune system. It has been shown to help people with advanced melanomas of the skin live longer, although it can also have some serious side effects. Some doctors now use it to treat melanomas of the eye as well, although its benefits against this cancer are still being studied in clinical trials.
Newer drugs such as nivolumab and lambrolizumab, which boost the immune response against cancer cells in a slightly different way, have shown even better results against skin melanomas in early studies. These drugs might prove to be useful against eye melanomas as well.
As researchers have learned more about some of the changes in cells that cause them to become cancerous, they have begun to develop 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 (and often less severe) side effects.
Most eye melanomas have been found to have changes in the GNAQ or GNA11 genes, which are part of the MAPK gene signaling pathway that helps cells grow. Selumetinib is a drug that targets the MEK gene, which is also part of the MAPK pathway. Selumetinib is the first drug that has been shown to slow the growth of advanced eye melanomas and help people live longer in a clinical trial. While it does not cure these cancers, it often causes them to shrink for a time. For now, this drug is only available through clinical trials.
Other drugs might also be useful in treating cancers with these gene mutations. For example, some early research suggests that sotrastaurin (AEB071), a drug that targets protein kinase C, might be effective against cells with a GNAQ mutation. This is now being studied in clinical trials.
Some other newer drugs, such as vemurafenib (Zelboraf®), dabrafenib (Tafinlar®), and trametinib (MekinistTM), 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.
Many other targeted drugs are already used to treat other types of cancer. Some of these drugs are now being studied for use against melanoma of the eye as well, including sunitinib (Sutent®), sorafenib (Nexavar®), vorinostat (Zolinza®), and everolimus (Afinitor®).
Other drugs target the blood vessels that allow tumors to grow. These are known as anti-angiogenesis drugs. One example is bevacizumab (Avastin®), which is already used to treat some other types of cancer. It may help prevent some of the side effects from radiation, which may help patients retain more vision after treatment. It is also being studied for use along with chemotherapy in people with advanced eye melanomas.
Last Medical Review: 09/13/2013
Last Revised: 02/11/2014