NEW YORK – Cancer researchers at the University of Miami's Sylvester Comprehensive Cancer Center, Moffitt Cancer Center, and University of Florida's Health Cancer Center have received a five-year, $3.95 million NIH grant to study the genomics underlying metastatic uveal melanoma.
Earlier research supported by two Florida State Team Science Awards flagged the involvement of two mutated proteins, Gaq and BAP1, in the progression and spread of uveal melanoma to the liver. Uveal melanoma is among the most common adult eye cancers and when aggressive, tends to spread to the liver. Despite the initial identification of Gaq and BAP1 mutations, the biological process driving the progression and spread of uveal melanoma hasn't been deeply studied, according to William Harbour, associate director for basic science at Sylvester, who is leading the NIH-funded project at the institution.
The other scientists on the research team include Keiran Smalley, director of the Melanoma and Skin Cancers Center of Excellence at Moffitt, and Jonathan Licht, director of the University of Florida Health Cancer Center. The NIH grant will allow these researchers to further elucidate the role of Gaq and BAP1 mutations in the spread of uveal melanoma and explore ways to inhibit these processes.
"Typically, people get a Gaq mutation first, but most of the time, the body gets rid of those proliferating cells and people end up with a nevus or a mole," Harbour said in a statement. "But sometimes these cancers break through the body's security measures, and one of those ways is through BAP1 mutations. We want to understand why these two mutations go together in uveal melanoma, because they really don’t pair up very often in other cancers."
The researchers have hypothesized that in the case of uveal melanoma, BAP1 mutations may reverse the body's ability to suppress Gaq-mutated cells, which in turn promotes cancer. Furthermore, they suspect that BAP1 mutations may allow uveal melanoma cells to hide in liver tissue from the immune system, which may be why this type of cancer so often spreads to the liver.
"There may be common signaling pathways in the eye and the liver," Harbour said. "These uveal melanoma cells could find a parallel environment in liver tissue that allows them to survive."
Through their research, Harbour and colleagues also hope to identify ways of stopping the spread of uveal melanoma. Toward this end, they will explore the ability of drugs such as HDAC inhibitors to stop uveal melanoma liver metastasis by degrading BAP1 activity.