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Researchers study breast cancer drug resistance with $1.5 million grant

Dr. James McCubrey. Photo by Cliff Hollis.
GREENVILLE, N.C.   (Feb. 11, 2003)   —   The National Institutes of Health and the National Cancer Institute have awarded two East Carolina University scientists a $1.5 million, five-year grant to identify signal transduction pathways in cells that become resistant to chemotherapy drugs used in treating breast cancer. Drs. James McCubrey and Richard Franklin are faculty members in the Department of Microbiology and Immunology at the Brody School of Medicine at East Carolina University in Greenville.

"It's a significant problem, especially for breast cancer patients, that when you treat them with chemotherapy drugs some of their cells will become resistant to the drugs that are designed to hinder the growth of the cancer," said McCubrey, primary investigator of the study.

Depending on the stage of breast cancer an person has, it may take five to 10 years following surgery and chemotherapy before the cancer resurfaces in another part of the body.

"One of the big problems when the cancer comes back is that many of the cells will now be resistant to the chemotherapy drugs that are available," McCubrey said. "Our study will look at the different mechanisms at the cellular level that are used to treat breast cancer and will evaluate the growth pathways that can be triggered to stimulate healthy cell growth or cell death for cancerous cells."

McCubrey and Franklin will look specifically at cellular reaction to the use of the chemotherapeutic drugs doxorubicin and paciltaxel. By learning more about the signal transduction pathways, specifically Ras/Raf/MEK/ERK and PI3K/AKT, and how they influence drug resistance, more information can be made available to physicians on the use of combinations of drugs to better treat breast and other cancers, McCubrey said.

The study will involve evaluation of breast cancer cells that were donated to the Michigan Cancer Foundation for research. McCubrey and Franklin will also genetically modify some of the cells as part of the study.

In the United States, breast cancer is the most common form of cancer among women, according to the National Cancer Institute. It is estimated that more than 180,000 new cases are diagnosed across the nation each year. Over a lifetime (80-plus years), American women have a one in eight chance of developing breast cancer, which is caused by mutated or amplified genes. Hereditary breast cancer accounts for just 10 percent of all cases. In 90 percent of these types of breast cancer, the mutations are related to the BRCA1 or the BRCA2 genes. Other genetic mutations account for the majority of sporadic or non-hereditary breast cancer.

ECU's study will also evaluate how the BRCA1 and BRCA2 genes regulate signal transduction pathways in cells.

This is McCubrey's second NIH grant since 1997. Over the past five years, he has received eight grants totaling more than $2.6 million from NIH, Monsanto, the N.C. Biotechnology Center and ECU and has published 68 articles related to these grants.

Over the past year, McCubrey and his colleagues have received several requests from British, French and American companies to write review articles for scientific journals and databases.

In addition to supporting studies, the grants are used to create graduate and post-doctoral fellowships. "It's very satisfying to have an opportunity to make some progress in the treatment of such a significant disease as breast cancer that causes hardship and suffering in so many lives," Franklin said. "These grants also help us support graduate students as they earn their Ph.D.s and help post-doctoral fellows as we work together on these studies. This really means a lot to our work and to the school."

While most laboratory research takes anywhere from 10 to 20 years before it has a clinical impact on patients, McCubrey feels this study could reveal valuable knowledge in treating patients in as little as five years.

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Contact: Jane Martin | 252-744-2481