New MSU drug offers hope to stop spread of skin cancer

Kim Kozlowski
The Detroit News

In a small lab at Michigan State University, researchers have discovered a potential drug that could stop the spread of melanoma, the deadliest form of skin cancer, by 90 percent.

Though the potential drug is still two to five years away from human trials, the discovery is being hailed as promising since the man-made, small-molecule compound shuts down a gene’s ability to produce RNA molecules and certain proteins in melanoma tumors, stopping the cancer from spreading.

The potential drug is showing promise not only for melanoma but possibly other cancers, such as breast cancer, said Richard Neubig, professor and chair of the MSU Pharmacology and Toxicology department and author of the study.

That’s because the compound treats a pathway in the melanoma cells that is also present in breast cancer cells.

“What we showed is we can very dramatically reduce the metastasis (the spread of cancer),” Neubig said. “We think the potential is tremendous and are excited about the possibilities.”

The findings were recently published in the journal Molecular Cancer Therapeutics after a 10 year-study.

While the discovery still has to go through clinical trials, those who have been touched by melanoma are hopeful about the future.

Among them is David Stanley, a Flint resident, who was diagnosed about 10 years ago with stage II melanoma and had to undergo surgery twice on his face. At the time, surgery was his only option, which he said was challenging.

“Anything we can do that is going to be a more effective treatment for a disease that is so disfiguring and (sometimes) fatal is a really good thing,” said Stanley, an MSU graduate who wrote a memoir about his battle with skin cancer. “The thing that makes this drug so promising is it shuts off the ability of the cancer cells to reproduce. ... If this works, in the big picture, it’s going to be groundbreaking.”

Decade in making

Skin cancer is the most common form of cancer, and there are several forms of skin cancer. Melanoma is most likely to grow, spread and potentially become fatal, according to the American Cancer Society.

There were 71,943 people in the U.S. diagnosed with melanoma in 2013, the most recent statistics available, according to the Centers for Disease Control and Prevention. Of those diagnosed, 9,394 died.

If the disease is caught early, the chance of death is 2 percent, Neubig said. But caught late, chances of death increase to 84 percent.

“The potential opportunity for our compound in patients is exciting because of how deadly the disease is once it has metastasized,” said Kate Appleton, an MSU postdoctoral student and an author of the study.

The study began a decade ago when Neubig was at the University of Michigan.

Then, Neubig and his fellow colleagues screened 2,000 compounds in an effort to find a chemical that would block a signaling pathway in melanoma since there aren’t drugs able to block that pathway, known as Rho MRTF. They found one compound that they used in mice injected with melanoma cells.

“But, unfortunately, that compound was too toxic,” Neubig said. “The mice died from the chemical — not the tumor.”

Neubig worked with Scott Larsen, a UM professor of medicinal chemistry, to modify the compound so it was less toxic.

Studies began on the compound at UM and continued at MSU when Neubig moved to the East Lansing university.

The next step

Some melanoma cells have the pathway activated that Neubig and his colleges were trying to block, while other cells do not. But the cells that do have this pathway activated spread fast, Neubig said.

Part of the study involved testing cells grown in Petri dishes to see if the compound would block the migration of the melanoma cells. Their work showed the compound was able to stop the migration of melanoma cells by 85-90 percent.

Additionally, the researchers were able to show the drug significantly reduced tumors in the lungs of mice with human melanoma cells, helping them find the new signaling pathway as a target in cancer.

Since not all patients have this signaling pathway turned on, the next step in the researchers’ work is to find out which patients would benefit most.

“Being able to look at this activity might be a way of identifying aggressive melanoma that needs to be taken care of right away,” Appleton said.