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 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 Research 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-Hodgkins lymphoma, leukemia and
melanoma.
At UNMC, Dr. Cavalieri will be working on the study with Eleanor Rogan,
Ph.D., a professor in the Eppley Research 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.