OMRF study finds potential target for ovarian cancer treatment

An Oklahoma Medical Research Foundation scientist has discovered that an overactive gene appears to play a role in the development of ovarian cancer and that it can be targeted to kill the cancer cells the gene is connected to.

The gene, SDHA, produces an enzyme called SDH that causes ovarian tumor cells to grow and migrate. OMRF scientist Magdalena Bieniasz, Ph.D., found that in research models, about 20% of ovarian tumors have large quantities of that enzyme.

“What this means is that in females, the tumors have a high metabolism and develop fast,” said Bieniasz, who joined OMRF in 2014 from the Huntsman Cancer Institute.

She called the gene a “doubleedged sword,” because while it promotes growth in ovarian tumors, tumors with high levels of SDH seem to respond more favorably to chemotherapy than those with low levels of SDH.

About 20,000 U.S. women are diagnosed with ovarian cancer annually, according to the American Cancer Society. Because women frequently overlook the early symptoms of ovarian cancer, patients are often not diagnosed until it has spread throughout the pelvis and abdomen. As a result, the five-year survival rate following diagnosis is about 50% – far below the survival rate for most other cancer types. Among women, it is the fifth-leading cause of cancerrelated death.

Previous research found a connection between a deficiency of SDH and rare cancer types as well as neurodevelopmental disorders. However, scientists had not yet studied the link between too much of the enzyme and ovarian cancer, Bieniasz said.

Bieniasz used a library of compounds and found that several, including a plant-based compound, that could improve killing ovarian cancer cells with high levels of SDH by disrupting their energy production.

“This tells us that targeting this gene could be part of an effective treatment in certain ovarian tumors,” said Bieniasz, whose lab is in OMRF’s Aging and Metabolism Research Program. “The next phase of this work is to optimize targeting the gene in ovarian tumors while minimizing effects on other cells.”

OMRF scientist Benjamin Miller, Ph.D., who chairs the program, said both discoveries advanced existing knowledge about ovarian cancer.

“These are important findings not only for the genetic connection Dr. Bieniasz has found but also for this very early indication regarding one piece of a potential therapy,” Miller said. “These insights reveal more about how ovarian cancer cells use energy and suggest new ways to target their metabolism for more effective treatment options.”

The findings were published in the journal Cancers. The study was supported in part by grant 1 P20 GM139763-01 from the Centers of Biomedical Research Excellence, a program of the National Institutes of Health that helps junior scientists establish independent research programs, and by NIH grant R21 CA264573-01A.