By age 80, the average woman has about a 10 percent chance of developing breast cancer. Billions of dollars have been spent on research into the disease, resulting in promising treatments and preventative measures. As it does in many medical fields, the Medical Center is helping lead the way in tackling this dreaded disease.
The Medical Center is the recipient of a Specialized Program of Research Excellence in breast cancer, a research grant funded by the National Cancer Institute, a division of the National Institutes of Health. SPORE's grants support multi-disciplinary programs of research on a specific cancer. The $10 million grant, distributed evenly over five years, is the only SPORE at the University and is the centerpiece of the Medical Center's research into breast cancer.
Awarded in 1995, the grant supports breast cancer research in the areas of genetics, information management, administration and education, explained Dr. Dirk Iglehart, associate professor in the department of pathology and one of the SPORE's administrators. Iglehart added that the grant funds six major research projects and involves almost every department in the Medical Center.
Breast cancer, like most cancers, is the result of uncontrollable cell division. Over time, this undifferentiated mass of cells inhibits normal tissue function and can spread to the rest of the body, often leading to death.
Researchers at the University are attacking the disease from a variety of angles. One strategy involves blocking blood vessel growth to the cancerous cells. Capillaries-the tiny vessels that allow nutrients exchange between blood and tissue-spread into tumor cells and enable them to continue their rapid and eventually harmful growth. Scientists at the University and beyond are looking at methods to stop this blood vessel growth-called angiogenesis-from occurring.
Dr. Charles Greenberg, associate professor of hematology and medical oncology, Dr. Kevin Peters, assistant professor of pharmacology and cancer biology and Mark Dewhirst, professor in the department of radiation oncology, are working on creating drugs that stop angiogenesis in tumor cells.
Angiogenesis is typically triggered through the action of receptor molecules that receive growth signals and cause blood vessels to spread. The researchers used fake receptors to absorb the growth signals and prevent them from reaching receptors actually capable of causing angiogenesis, Dewhirst said. In a paper accepted for publication by the Proceedings of the National Academy of Science, Dewhirst, Peters and their coworkers found that by using their fake receptors in mice they were able to halt the spread of cancer.
Both Peters and Dewhirst, however, said that the fake receptors are not yet ready for clinical trials in human patients.
Another area of the SPORE grant focuses on the two breast cancer susceptibility genes, named BRCA1 and BRCA2. The latter gene was discovered at the University in 1995. Carriers of mutated copies of these genes are at very high risk of developing breast cancer, although cases in which susceptibility is inherited account for only five percent of all cases.
Jeffrey Marks, associate research professor in the division of general surgery and one of the scientists currently researching the operation of these genes, said that when functioning correctly, the genes likely work toward proofreading DNA, which contains information telling the cell when and how to divide. Mutated genes do not correct mistakes that occur in the DNA strand, leading to improper divisions and tumor development.
Marks' most recent work examined the regulation, or the timing, of the BRCA2 gene's expression, and may help tie inherited risk factors to those that appear during the life of the patient. "Looking at gene regulation gives us a segue into looking at sporadic cancers," he said.
SPORE researchers also focused on mimicking estrogen, the female hormone that induces breast growth. The drug tamoxifen, an estrogen-mimicking compound, recently leapt into national headlines thanks to clinical trials that demonstrated the drug's ability to reduce the risk of developing breast cancer. By blocking receptors that allows cells to interact with other compounds, tamoxifen halts the uncontrolled growth of the cells that result in cancerous tumors.
Tamoxifen has, however, been found to increase the risk of uterine cancer and thromboembolism, the blocking of blood vessels by debris from blood clots in other parts of the body. To that end, Donald McDonnell, associate professor of pharmacology and cancer biology, is researching the related drug raloxifene, which appears to have the same preventive measures as tamoxifen without its side effects.
If these hormones do have the ability to prevent or reduce risk, "there will be a very large call" to give the drugs to women who carry the BRCA1 or BRCA2 genes, Marks said. He added that researchers and ethicists are wrestling with the ethical issues of genetic testing, which is required to determine who carries the susceptibility genes.
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