(SALT LAKE CITY) - Eye cancer took the life of author and neurologist Oliver Sacks last year, bringing attention to the rare and deadly disease. Scientists have tried to develop precision treatments against cancers like this one, but the mutations that cause them have proven difficult to block with drugs.
Now, a team led by scientists at Huntsman Cancer Institute at the University of Utah, University of Utah School of Medicine, and Navigen, Inc., report a new treatment that shows promise against the hard-to-treat cancer. They found that the mutation relies on a protein, ARF6, to distribute cancer-promoting signals. Further, a drug that blocks ARF6 inhibits eye tumors in mice. The research appears in Cancer Cell online on June 2.
"We completely bypass the mutations in Gaq oncogenes that have been so hard to target, and have found a different strategy for slowing the disease," says Dean Li, M.D., Ph.D., Huntsman Cancer Institute investigator and H.A. and Edna Benning Endowed Professor of Internal Medicine at the Eccles Institute of Human Genetics. He and Kirill Ostanin, Ph.D., senior director at Navigen, Inc., were senior authors on the study.
A new understanding of how eye cancer works led to the unexpected finding. Ordinarily ARF6 works to relay molecular signals within healthy cells. Here, the scientists report that a mutation that causes eye cancer hijacks ARF6, redirecting it to relay signals to cancer promoting pathways. Blocking ARF6 with the drug inhibits dissemination of the cancer message.
"In eye cancer, ARF6 is like a traffic cop at a major intersection that directs the traffic of cancer signals down a number of paths. The drug forces ARF6 to hold back traffic," says Li. "We think this same treatment strategy could also work against other cancers." These include skin, breast, brain, renal and additional cancers in which ARF6 is known to play a role in the disease. Li and Ostanin are now leading studies to further optimize and test the drug. Further, Li is investigating whether the general strategy, inhibiting proteins that distribute cancer signals, could be applied to more broadly.