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UNC geneticists create the first mouse model of ovarian clear cell carcinoma; show how a known drug can suppress tumor growth.

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Terry Magnuson, PhD/ Photo by Max Englund, UNC Health Care)
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Ron Chandler, PhD

In the battle against ovarian cancer, 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, PhD, 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 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. 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,” 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 today in the journal Nature Communications, was spearheaded by Ron Chandler, PhD, a postdoctoral fellow in Magnuson’s lab. 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. Chandler began researching the gene’s precise function in that disease and found that deleting it in mice did not cause tumor formation or tumor growth.

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