Medical experts with specialty in eye care recently revealed that a compound extracted from the Christmas berry primrose plant may help stop the growth of metastatic uveal melanoma, a rare and aggressive cancer of the eye.
Doctors diagnose about 2000 adults with uveal melanoma, every year. In half of cases, the disease metastasizes to the liver. For these, patients treatment options are scarce.
According to the findings, published in the Molecular Cancer Research journal, uveal melanoma (UM) is the most common eye cancer in adults. The cancer forms in melanocytes, the cells that make pigment. Although the condition differs from melanoma of the skin, both cancers are lethal.
Uveal melanoma accounts for about 5 percent of all melanoma cases. Surgery or radiation is the go to treatment for patients with primary (UM) that has not spread to other parts of the body. The cancer most often travels to the liver. Once the cancer has spread, patients often only have a year or so to live as no effective therapies yet exist.
“I'm very optimistic,” said Jeffrey Benovic, PhD, Thomas Eakins Endowed Professor of Biochemistry & Molecular Biology at Thomas Jefferson University and an Associate Director with the Sidney Kimmel Cancer Center (SKCC), who led the new work. “If the results are confirmed in animal models and eventually humans, it could offer a new way to treat metastatic uveal melanoma, patients down the road,” he added.
The researchers tested whether a compound derived from an ornamental plant in the primrose family known as Ardisia crenata, might be able to fight the disease.
The compound, called FR900359, or simply FR, was discovered 30 years ago from the plant's leaves. FR works by blocking a particular type of G protein that sits on a cell's membrane, called Gq – an important signaling molecule. But a subset of these proteins are mutated in uveal melanoma, turning on a molecular pathway that leads to cancer growth.
Dominic Lapadula, a graduate student in Dr Benovic's lab, grew three different types of uveal melanoma cells that have the cancer-spurring mutations in the lab. Then he treated the cells with FR.
“We didn't expect it would work because previous research suggested a related compound called YM-254890 did not inhibit the mutated forms of the proteins found in uveal melanoma,” said Dominic Lapadula. “But lo and behold, FR very effectively blocked the growth of the uveal melanoma cells.” When the uveal melanoma cells were treated with small amounts of FR, the cells appeared to revert from cancer cells to typical melanocytes. “FR appears to be able to help reset the cells back to their normal state,” Dr Benovic said. “Ideally that's what you want.”
According to the research conducted by experts, higher doses of FR killed the cells, and the results suggest the compound could be an effective drug to treat uveal melanoma one day.
“I'm hopeful FR and related compounds will reset the cancer cells in the mouse model as it did in the cells we grew in the lab,” Dr Benovic said, “getting it one step closer to testing in humans.”
Karen E. Knudsen, PhD, Enterprise Director of the (SKCC), said of the study, “This outstanding work is part of a larger effort within our Center to develop new strategies for combating uveal melanoma. As one of the few cancer centers specializing in this aggressive cancer type, Dr Benovic and team work closely with clinical partners within SKCC to fast track discoveries into the translational setting.”
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