According to the American Cancer Society, the majority of patients with primary eye cancer will survive the disease. The survival rate for other types, like iris melanoma, can even go as high as 95 percent. However, when the cancer becomes metastatic (when the malignant cells spread elsewhere in the body to form new tumors), this rate can drop significantly. Creating a way to delay the development of eye cancer is thus crucial.
In a discovery by a team of researchers in Germany, alongside colleagues from the US, one plant could be the key to such a method. The coralberry, originally from Korea, is a beautiful, bright red fruit that makes for an ideal decoration, especially during holidays.
In the medicine world, however, this plant gives valuable insight to a mechanism that could potentially slow down cancer. Researchers found out that its leaves contain bacteria that produce a compound called FR900359 (FR), something that has been on the radar of the science community for three decades.
The Value Of FR To Uveal Melanoma Treatment
The coralberry adorns many German living rooms during the winter months. But more than an ornamental plant, the bacteria in its leaves produce a natural insecticide called FR. While that sounds like a cryptic toxin, a study claims that FR could ease asthma more effectively than standard medication. More surprisingly, the substance that protects the coralberry from insects may play a key role in a completely different field – as a potential cure for uveal melanoma, the common and aggressive kind of eye cancer.
The cancer starts at the layer of pigmented cells of the eye that includes the iris. It represents about three to five percent of all melanoma cases, and is fatal in about half of the patients who develop it. Uveal melanoma doesn’t have a strong link to ultraviolet ray exposure, unlike skin melanoma. However, researchers say people with fair skin and blue or green eyes are at higher risk of developing the cancer.
The G Protein Mechanism
Professor Kendall Blumer of the Washington University in St. Louis led a study on the properties of FR and its effect on cancer cells. The results of the paper appear in the journal Science Signaling. She states that in about half of patients, the tumor from ocular melanoma spreads to other organs and grows aggressively. She further explains that there are fairly new targeted treatments, including immune therapies for skin melanoma that increase the survivability of patients, even after tumors have metastasized. However, these treatments don’t seem to have the same effect on uveal melanoma. That is why scientists are looking for new therapeutics in this certain type of cancer.
For decades, researchers have been analyzing the overactive signaling molecules in uveal melanoma but have had little clinical progress in shutting them down. The protein commonly found in this specific type of tumor is called G alpha q, which belongs to a class of molecules known as G proteins. When such substances develop genetic errors that switch them on permanently, cancer can result.
While active, the G alpha q binds to another molecule that keeps it active and the signaling cascade flowing constantly. In the quest for treatments for uveal melanoma, researchers have performed various procedures to stop pieces of the cascade started by G alpha q. Thus far, no strategy has succeeded in improving patient condition.
Trapping Gq Proteins
Fortunately, the new findings support a surprisingly simple solution. Rather than shutting down parts of the cascade that G alpha q activates, the researchers proved they could simply wait for the protein to release the molecule that keeps it awake. This random split happens at a low rate, but if a drug is present that can trap G alpha q while it is sedentary, the scientists thought that the entire signaling cascade that causes cancer would gradually stop, one protein at a time.
This is where the natural compound FR – present in a member of the primrose family of plants – become extremely useful. FR can bind itself firmly to dormant G alpha q, ensnaring it in its deactivated form. When the protein just happens to switch off on its own, FR comes to trap it there.
Preventing Gq Proteins From Activating
As it turns out, scientists don’t have to forcefully turn off the cancer-causing form of G alpha q. Author of the study and assistant professor of biochemistry and molecular biophysics Michael D. Onken says, “It just turns itself off every now and then on its own. But it then can be locked down with FR, and that’s enough to shut down tumor cell growth.”
Indeed, the study reveals that FR can destroy human uveal melanoma cells growing in the lab. What’s more, it seems to also have the ability to revert a subset of those cells back to a state similar to normal pigmented cells of the eye.
Halting Cell Division
The science community already knows that FR can prevent Gq proteins from activating by holding onto them. This year, however, Dr. Kostenis and his research team from Germany found something no one would have suspected – that FR can also halt cell division. The feat seemed impossible at first, explains Dr. Evelyn Gaffal, now at the University of Magdeburg. This is important as uveal melanoma has two Gq proteins that are permanently active, causing a mutation that divides cells continuously.
In the same way as before, FR holds onto the protein to prevent it from activating. As time goes on, more Gq proteins become dormant again, potentially decelerating the development of uveal melanoma. The next step now is to ensure that FR goes only for tumor cells and not healthy tissues.
G proteins can be found throughout the body, so creating ways to deactivate them could also be relevant for other disorders, such as cholera and Sturge-Weber Syndrome, a neurological disorder that often causes muscle weakness and seizures.
Furthermore, evidence associates such proteins to common diseases affecting large numbers of people, including high blood pressure and asthma. While scientists are trying to dig deeper into the effect of FR in the cells of mice with cancer, it may not take long before it can be tested and approved for human patients.
