Researchers Pinpoint Two Genes (ARID1A and PIK3CA ) That Triigger IL-6 and Cause Severest Form of Ovarian Cancer; Show How Known Drug (BKM120) Can Suppress Tumor Growth

In the battle against ovarian cancer, University of North Carolina (UNC) School of Medicine researchers have created the first mouse model of the worst form of the disease and found a potential route to better treatments and much-needed diagnostic screens. Led by Terry Magnuson, Ph.D., the Sarah Graham Kenan Professor and Chair of the Department of Genetics, a team of UNC genetics researchers discovered how two genes interact to trigger cancer and then spur on its development. "It's an extremely aggressive model of the disease, which is how this form of ovarian cancer presents in women," said Dr. Magnuson, who is also a member of the UNC Lineberger Comprehensive Cancer Center. Not all mouse models of human diseases provide accurate depictions of the human condition. Dr. Magnuson's mouse model, though, is based on genetic mutations found in human cancer samples. Mutations in two genes -ARID1A and PIK3CA - were previously unknown to cause cancer. "When ARID1A is less active than normal and PIK3CA is overactive," Dr. Magnuson said, "the result is ovarian clear cell carcinoma 100 percent of the time in our model." The research also showed that a drug called BKM120, which suppresses PI3 kinases, directly inhibited tumor growth and significantly prolonged the lives of mice. The drug is currently being tested in human clinical trials for other forms of cancer. The work, published online on January 27, 2015 in Nature Communications, was spearheaded by Ron Chandler, Ph.D., a postdoctoral fellow in Dr. Magnuson's lab. Dr. Chandler had been studying the ARID1A gene, which normally functions as a tumor suppressor in people, when results from cancer genome sequencing projects showed that the ARID1A gene was highly mutated in several types of tumors, including ovarian clear cell carcinoma. Dr.
Login Or Register To Read Full Story