You may never have heard of ocular (eye) melanoma, but if you’ve made a donation to the annual Melanoma Miles for Mike Run/Walk event held in Washington each spring, you are helping to unlock some of the mysteries of this disease — and close to home, too.
Dr. J. William Harbour, an ophthalmologist working at Washington University’s School of Medicine, has received the Mike Revers Research Grant (a $25,000 award) from the Melanoma Research Foundation.
Mike Revers is the late husband of Washington native, Beth (Mayer) Revers Castle, and late son-in-law of Dick and Cindy Mayer, Washington.
The family founded the Melanoma Miles for Mike nonprofit (www.melanomamiles.org) back in 2007 to uphold a promise Beth made to Mike before he died earlier that year, just shy of his 29th birthday: She would do what she could to raise awareness of melanoma and its risk factors and also raise funds for research to help others who are diagnosed.
Since 2007, Melanoma Miles for Mike has raised over $130,000 for melanoma research and had five $25,000 research grants created in Mike Revers’ name by the Melanoma Research Foundation.
If you’ve supported Melanoma Miles for Mike and ever wondered how much of a difference your donation is making, Dr. Harbour has good news.
For the last several years, his research has been focused on improving survival rates for ocular melanoma (OM) patients.
“The most pressing problem with ocular melanoma is not how to treat the primary tumor — we have good surgical techniques for controlling them — but it’s this cancer’s tendancy to spread,” said Dr. Harbour. “Even when we think we got it all, the patient can end up years later with it in their liver, lungs . . .
“Understanding what causes it to metastasize (spread) and how to develop ways to identify which patients will develop matastisis” is what Dr. Harbour’s team specifically has been studying.
The outcome of their work can be lifesaving. As many as half of patients who develop OM will have it metastasize — the most common cause of death for cancer patients.
Back in 2010, Dr. Harbour’s team, working with the genome center at Washington University, identified the BAP1 gene as being linked to the spread of ocular melanoma to the rest of the body.
Then earlier this year, Dr. Harbour’s team announced they had developed a genetic test that can accurately predict whether ocular melanoma will metastasize.
“It’s now used in 70 centers around the world,” Dr. Harbour noted.
The team’s newest grant funding, a portion of which was provided through the Melanoma Miles for Mike, will allow Dr. Harbour and his colleagues to continue that research through to clinical trials on different treatment approaches.
Ocular melanoma is the most common form of eye cancer with over 2,000 adults in the United States being diagnosed with it each year, said Dr. Harbour.
It occurs most commonly in light-skinned, light-haired people with light eyes, although it is not related to sun exposure, according to the Ocular Melanoma Foundation (www.ocularmelanoma.org).
“Although produced from the same cells in the body, called melanocytes, OM is different from skin (or cutaneous) melanoma and is not related to sun exposure. Ocular Melanoma is the second most common type of melanoma after cutaneous and represents about 5 percent of all melanomas,” the website reads.
Half of patients who develop OM will be diagnosed on a routine annual eye exam, said Dr. Harbour. They won’t have any symptoms.
There can be symptoms, however — experiencing a blurring or flashing light or a black spot in your vision, Dr. Harbour noted.
Treatment varies once someone is diagnosed with OM, depending on how large or small the tumor is. If it’s too large, the entire eye may have to be taken out, said Dr. Harbour, but if it’s small enough, patients can receive something called plaque radiotherapy to kill the tumor.
“Ninety percent of people will be given a radiation treatment that involves taking a small device that looks like a bottle cap made of gold with radioactive seeds on one side and sewing it onto the outside of the eye,” Dr. Harbour explained.
“We leave it there for several days, and 95 percent of the time, it will kill the tumor, although there may be some vision loss.”
A gene is something that is encoded in each person’s DNA. It’s a blueprint for a specific protein, which carries out a specific function, Dr. Harbour explained.
The purpose of the BAP1 gene, his team found, is to act as a metastasis supressor — to prevent the spread of OM cancer cells to other parts of the body. When there is a mutation to the BAP1 gene, metastasis occurs.
Dr. Harbour compared the mutation of a gene to changing letters in a word.
“If one letter is changed, is mutated, that changes the entire meaning of the word,” he said.
“So if we can identify which protein is mutated, we can design a medication that attacks it,” he said.
These medications are called HDAC inhibitors.
Some of these medications already were on the market and commonly available when Dr. Harbour’s team made their discovery. One is an anti-seizure medication that is well-tolerated, he noted.
“Now we take the high-risk patients and start a clinical trial to put them on one of these HDAC inhibitors to see if it delays the spread of the cancer,” said Dr. Harbour.
In the future, these HDAC inhibitor drugs will be a starting place for OM patients, said Dr. Harbour, but he expects that better kinds of drugs that target the BAP1 mutation more specifically will be found.
“That will take several years of intense research with more targeted compounds,” he said.
‘A Very Important Gene’
Dr. Harbour’s discovery of the BAP1 gene mutation back in 2010 was monumental for his own research and also for researchers working on other types of cancer, it turns out.
Once Dr. Harbour’s team identified the BAP1 gene mutation, other cancer researchers looked for and found the same thing in their patients.
“It ends up it’s a very important gene,” Dr. Harbour remarked.
For some patients, the BAP1 gene becomes mutated inside the tumor, but there are other patients who inherit the mutation, Dr. Harbour noted.
A simple blood test will show if someone inherited the mutation, and the benefit to knowing this, Dr. Harbour explained, is that a person can modify his or her lifestyle to try to prevent developing OM cancer.
Dr. Harbour’s team also is continuing to look for other gene mutations present in OM because the BAP1 mutation is only present in 40 percent of OM cases.
Valuable, Critical Funding
Dr. Harbour, who has been researching OM since 1998, said funding he receives from private foundations is critical to his work and, for that matter, any researcher.
“When research is very mature, you can get grants from the federal government . . . but those are slow in coming and take many years,” said Dr. Harbour.
“Even if I came up with a discovery today, it would take two years, if I was lucky, to get any money.”
That is why grants like the Mike Revers Research Grant awarded from the Melanoma Research Foundation are so valuable, he said. They give him the funding he needs to mature and advance his research to the point that he will qualify for federal funding.
“The unique role of these private foundations is that they can much more quickly get money to new ideas to get them going,” said Dr. Harbour.
“The other thing they do is, when you apply for a federal grant, you have to have a lot of data behind your idea, and where will you get that preliminary data?
“Without this money, you would never get anywhere.”