Revealing Ovarian Cancer’s Deadly Secrets

When it comes to ovarian cancer, any progress is good news. Since ovarian cancer produces few or no symptoms during its early stages, 70 percent of patients aren’t diagnosed until after the tumor has grown or spread to other parts of the body.

Scientists in the Comprehensive Cancer Center are trying to give physicians new diagnostic and treatment tools to help their patients with ovarian cancer. They are targeting genes responsible for tumor cell signaling and the growth of new blood vessels that feed the growing tumor. Understanding how these genes work could provide clues to ovarian cancer’s deadly secrets.

Kathleen Cho and Ronald Buckanovich Photo: Scott Galvin

A research team directed by Kathleen R. Cho, M.D., a professor of pathology and of internal medicine, is focusing on two defective cell-signaling pathways that lead to ovarian endometrioid adenocarcinoma, the second most common type of ovarian cancer.

“In the last 30 years, we haven’t done a lot to improve the survival of ovarian cancer patients,” Cho says. “This study has the potential to improve our understanding of early ovarian cancer.”

Researchers in Cho’s lab analyzed gene mutations and signaling pathway defects found in human ovarian tumor cells, and then created a strain of genetically engineered mice with the same defects to see if ovarian tumors would develop. In all the mice altered to possess both pathway defects, ovarian tumors developed rapidly and often metastasized.

Currently, Cho is using the mice developed in her lab for preclinical testing of a drug called Rapamycin to see if it can inhibit the defective cell-signaling systems involved in ovarian endometrioid adenocarcinoma.

Ronald Buckanovich, M.D., Ph.D., an assistant professor of internal medicine and of obstetrics and gynecology, is attacking ovarian cancer on a different front. He has identified more than 70 biomarkers that are found only in the cells of blood vessels running through ovarian tumors. By analyzing the biomarkers, Buckanovich and other scientists were able to identify genes that are active in tumor vascular cells.

“When these genes are highly expressed, we suspect it may be a sign of a tumor that’s able to grow blood vessels more efficiently and therefore is more aggressive,” Buckanovich says.

If he can prove that these markers are specific to ovarian tumors, Buckanovich believes it may be possible to develop drugs that target the blood vessels and strangle the tumor.

—Nicole Fawcett and Anne Rueter

For an expanded version of the story:
www.med.umich.edu/opm/newspage/2007/ovarian.htm

www.med.umich.edu/opm/newspage/2007/ovariancancer.htm