V. Craig Jordan, OBE, Ph.D., D.Sc., of Fox Chase Cancer Center has received a $10.7 million grant from the Department of Defense Breast Cancer Research Program for a Breast Cancer Center of Excellence focused on developing a new treatment model for breast cancer to reverse the eventual development of resistance to anti-estrogen therapy. The five-year multidisciplinary project, intended to encompass both laboratory research and clinical trials, involves scientists and physicians at Fox Chase and three other institutions, representing four task teams.
"The DoD Breast Cancer Research Program is pleased to support this innovative project by Dr. Jordan, his collaborators and Fox Chase Cancer Center to address a critical issue in breast cancer--the identification of new therapeutic drugs to treat women with breast cancer," said Col. Janet R. Harris, M.S.N., Ph.D., director of the Congressionally Directed Medical Research Programs administering the DoD Breast Cancer Research Program. "Through this project, new treatments will be brought from the laboratory to stage I and II clinical trials, facilitating the process for making new breast cancer therapeutic drugs available sooner."
This is Fox Chase's second Center of Excellence grant received in five years. In 2001, the Department of Defense awarded a $6 million dollar grant for the development of the nation's first Behavioral Center of Excellence for Breast Cancer Research.
Medical oncologist Lori J. Goldstein, M.D., director of Fox Chase's multidisciplinary Breast Evaluation Center, is Jordan's co-principal investigator for the new Center of Excellence grant. Jordan is vice president and scientific director of medical science at Fox Chase and holds its Alfred G. Knudson Jr., M.D., Ph.D., Chair in Cancer Research.
Jordan is known as the "father of tamoxifen" for his seminal work that led to the validation of tamoxifen as a therapy targeted to treat breast cancer and the first-ever drug to prevent breast cancer. Used for breast cancer treatment since the 1970s, tamoxifen is also the most widely used drug to treat breast cancer.
Much of Jordan's 35-year research career has focused on "designer estrogens" such as tamoxifen and newer drugs. Classed as selective estrogen-receptor modulators, or SERMs, they act like the hormone estrogen in some ways but not in others. These drugs can bind to the hormone receptors found in breast cells and thus block the effects of natural estrogen, which can promote breast cancer.
About two-thirds of breast cancers test positive for hormone receptors, so for many breast cancer patients, treatment with tamoxifen or newer drugs (such as aromatase inhibitors that stop estrogen production in postmenopausal women) can slow or stop the growth of cancer cells. Tamoxifen can also block the effects of natural estrogen in healthy breast cells, helping reduce the risk of breast cancer in women at high risk of the disease.
"In the past 25 years, the estrogen receptor has proven to be an important target for the treatment of breast cancer," Jordan explained. "However, there is a need for a new strategy to reverse the eventual development of antihormonal drug resistance, to ensure that effective agents can ultimately be used indefinitely."
The research to be conducted under the DoD grant takes advantage of the discovery that breast cancer cells devise complex survival strategies in response to estrogen-blocking drugs. These survival strategies allow cancer cells to overcome the protection the drugs confer.
However, Jordan's laboratory studies have shown that these drug-resistant cells can now be killed by tiny doses of actual estrogen. In resistant cancer cells, the estrogen no longer stimulates growth but instead triggers rapid programmed cell death--a process called apoptosis that allows aging or mutated cells to self-destruct.
Fox Chase researchers will work with the task teams and biostatisticians at Georgetown University's Lombardi Comprehensive Cancer Center in Washington, D.C., and Translational Genomics Research Institute in Phoenix, Ariz., to create a unique subcellular map of the new biology of estrogen that results in the rapid apoptosis. Then Fox Chase and the task team at Johns Hopkins University will conduct phase I and II clinical studies to evaluate estrogen-induced apoptosis in the tumor.
"The centerpiece of our effort is the clinical trials consortium enhanced with consumer advocate participants from Y-ME National Breast Cancer Organization, the Susan G. Komen Foundation, National Breast Cancer Coalition and Research Advocacy Network" Jordan said. "No single site or clinical organization alone can recruit the necessary number of patients for these clinical trials without the partnership of advocates to encourage eligible women to take part and to aid in providing the education and support they need.
"We will rapidly export our preliminary clinical finding to the Eastern Cooperative Oncology Group, which will establish the dose of short-term estrogen treatment necessary to be given to patients," Jordan added.
Jordan's published studies of tamoxifen and other designer estrogens have made him one of the top 20 most-cited breast cancer researchers over the past decade. He was the first scientist to demonstrate tamoxifen's ability to prevent breast cancer in laboratory rats. His pioneering work guided the evolution from preclinical lab studies to clinical research on the drug. Jordan also was instrumental in the development of the estrogen-modulating compound raloxifene, originally approved for osteoporosis and now shown to match tamoxifen in reducing breast cancer risk in postmenopausal women.
His awards include the General Motors Cancer Research Foundation's 2003 Charles F. Kettering Prize, the American Cancer Society's 2002 Medal of Honor, the 2001 Bristol-Myers Squibb Award for Distinguished Achievement in Cancer Research and the first Brinker International Breast Cancer Award for Basic Science from the Susan G. Komen Foundation in 1992. In 2002, Queen Elizabeth II named him an Officer of the Most Excellent Order of the British Empire (OBE) for services to international breast cancer research.
The Department of Defense grant is part of the Congressionally Directed Medical Research Programs, which administers funds for peer-reviewed research directed towards specific diseases and supports research that positively affects the health and well-being of all Americans.
The Department of Defense Breast Cancer Research Program is the second largest funder of breast cancer research, second only to the National Institutes of Health. The DoD BCRP Center of Excellence Award funds model projects that combine talents of an innovative leader, renown researchers from multiple institutions, outstanding clinicians from care and testing centers, with the strength of will from breast cancer survivors. More about the Department of Defense specific disease research is on website http://cdmrp.army.mil.
Fox Chase Cancer Center was founded in 1904 in Philadelphia as the nation's first cancer hospital. In 1974, Fox Chase became one of the first institutions designated as a National Cancer Institute Comprehensive Cancer Center. Fox Chase conducts basic, clinical, population and translational research; programs of prevention, detection and treatment of cancer; and community outreach. For more information about Fox Chase activities, visit the Center's web site at www.fccc.edu or call 1-888-FOX CHASE.