UNMC researchers land $5.6 million grant









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Eleanor Rogan, Ph.D., and Ercole Cavalieri, D.Sc.

A UNMC cancer researcher Ercole Cavalieri, D.Sc., is heading a $5.6 million multi-institutional research study to investigate the role estrogen plays in causing breast cancer and to look for new approaches to detecting and preventing the disease.

The four-year grant is called the Breast Cancer Center of Excellence Award and comes from the Department of Defense Breast Cancer Research Program. It is titled, “Estrogen-induced Depurination of DNA: A Novel Target for Breast Cancer Prevention.”

Scientists from five other institutions will be involved in the project. They include the Fox Chase Cancer Center in Philadelphia, the Stehlin Foundation for Cancer Research in Houston, the University of Virginia Health Sciences System in Charlottesville, the University of Memphis and the Mayo Clinic in Rochester, Minn. A total of 28 institutions applied for the grant.

“This grant was a perfect fit for our research group. The members belong to a National Cancer Institute group that was formed in 1997 and meets twice a year,” said Dr. Cavalieri, a professor in the Eppley Institute who is serving as principal investigator on the study. “We have a novel approach to cancer in general. Since we see a common origin of cancer – estrogen, we think that prevention of cancer is a relatively simple problem.

“Estrogen can become carcinogenic only when natural mechanisms of protection do not work properly in our body. In fact, if these protections go away due to genetic, lifestyle or environmental influences, then cancer can result. This is what we already know. Now – with this grant – we want to take things a step further and try to prevent it from happening.”

Dr. Cavalieri said the group believes that a specific oxidated metabolite called estrogen-3,4-quinone reacts with DNA to produce specific mutations that trigger cancer. They believe that this same metabolite is responsible for most common forms of cancer, including breast, ovarian, colon, pancreas and endometrial cancer, as well as non-Hodgkin’s lymphoma, leukemia and melanoma.

At UNMC, Dr. Cavalieri will work on the study with Eleanor Rogan, Ph.D., a professor in the Eppley Institute and a longtime research colleague. Together, Drs. Cavalieri and Rogan have six current research grants totaling more than $10.7 million. The two have each spent nearly 30 years of their careers studying the origin of cancer.

Dr. Cavalieri said the UNMC portion of the study will involve experiments on rats and animal tissue to try to determine if specific antioxidants can possibly inhibit the process of cancer initiation. In addition, they hope to work with cancer patients on a new technique for determining breast cancer risk.

As the study evolves, the scientists will initiate a large-scale human breast cancer trial, which will include women taking antioxidants.

“This is great recognition for the cutting edge research of Drs. Cavalieri and Rogan and their contributions to understanding the fundamental causes of breast cancer. They are truly recognized internationally for their understanding of this disease,” said Ken Cowan, M.D., Ph.D., director of the UNMC Eppley Cancer Center. “This grant will allow them to push forward on their research at a faster pace to help them determine which women are genetically at risk for developing breast cancer and targeting new therapies to prevent this disease.”

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