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The newspaper of The Johns Hopkins University October 18, 2004 | Vol. 34 No. 8
$10 Million to JHU for Study of Breast Cancer Spread

Collaborators include U. of Maryland and M.D. Anderson Cancer Center

By Vanessa Wasta
Johns Hopkins Medicine

The Johns Hopkins Kimmel Cancer Center has won a five-year $10 million government grant that will bring together national breast cancer experts to find new ways to halt metastasis, an elusive process that causes cancer cells to spread throughout the body and is the cause of death in most cancer patients.

"New technologies and the revolution in gene science have jump-started our understanding of how breast cancer cells spread," says Saraswati Sukumar, Barbara B. Rubenstein Professor of Oncology at the Johns Hopkins Kimmel Cancer Center and principal investigator of the grant. "Now, we are pooling our knowledge and resources to solve important problems plaguing every cancer patient of whether their disease will return and how to fight the spreading disease."

The grant, funded by the U.S. Department of Defense, will establish a Center of Excellence based at Johns Hopkins with collaborators at the University of Maryland Greenebaum Cancer Center, the University of Texas M.D. Anderson Cancer Center in Houston and Genzyme Biotechnologies. Breast cancer survivors will actively participate in project development, oversight and disseminating information on program goals and research results.

Sukumar will screen metastatic tumors for key molecular signatures that distinguish them from nonmetastatic tumor cells. Current cancer drug therapies have been unsuccessful in routinely preventing and eliminating those metastatic breast cancer cells that take root in other parts of the body.

"Molecular targets that are specific for metastatic cells may provide the foundation for developing new breast cancer drugs tailored to attack these cells," Sukumar says. With collaborator Steve Madden at Genzyme Biotechnologies, she will use a gene search tool to build a panel of breast cancer markers with high potential for identifying tumors capable of metastasizing, which also could serve as targets for drug development and other such therapies.

Other molecular targets may be teased out by attaching small proteins to bacterial viruses and mixing them with blood and tissue samples from metastatic breast cancer patients. M.D. Anderson's Renata Pasqualini, professor of cancer biology and medicine, will use this technique, called "phage display," to find proteins specific to metastatic cells.

Sukumar's colleagues at the University of Maryland Greenebaum Cancer Center will focus on designing new therapies using molecular modeling and high throughput screening technology to identify promising new compounds that interact with the molecules discovered by Sukumar and Pasqualini.

Angela H. Brodie, a Greenebaum Cancer Center researcher and professor of pharmacology and experimental therapeutics at the University of Maryland School of Medicine, notes that "a major problem with all tumors is that they can devise ways to survive the treatment that patients receive. They can adapt and grow even during the therapy. Our strength," she says, "is in new drug development for breast cancer, targeting those elements that cause or stimulate the growth of tumors."

Brodie's research has involved the discovery and development of a new class of drugs known as aromatase inhibitors, which help to prevent recurrence of breast cancer in postmenopausal women by reducing the level of estrogen produced by the body. According to Brodie, these inhibitors are proving to be more effective than the standard breast cancer drug, tamoxifen. She has focused on steroid biochemistry and the endocrinology of prostate cancer as well as breast cancer and other estrogen-mediated diseases.

Grant money also is expected to speed development of a therapeutic vaccine for breast cancer. Johns Hopkins cancer researchers Leisha Emens, an assistant professor of oncology, and Elizabeth Jaffee, Broccoli Professor of Oncology, say molecular discoveries will suggest ways to re-educate the immune system to target certain antigens found on metastatic cancer cells. Emens and Jaffee currently lead a clinical trial testing genetically engineered tumor cell vaccines against breast cancer.

To measure the response of newly developed drugs and immunotherapy tactics, Zaver Bhujwalla, professor of radiology and oncology at Johns Hopkins, will develop ways to use magnetic resonance spectroscopy and imaging to track the location of cells with targeted molecular alterations and immune signals. Her molecular imaging program uses noninvasive techniques to find the metabolic and molecular signatures of metastatic cancer cells. These techniques will reveal far smaller tumor deposits than standard imaging methods, enabling investigators to evaluate the success of new therapies.

Sukumar also will work with the Johns Hopkins Department of Pathology to establish a tissue-donation program to populate a bank of metastatic breast cancer tissues available for gene analysis.

"Scores of scientists have entered the breast cancer research field due to funding from the Department of Defense," Sukumar says. "Now, the creation of this Center of Excellence program has made it possible to bring some of the world's experts in this field together to make a major impact on a deadly aspect of this disease."

The Department of Defense began its cancer program in 1994 with $100 million in grants for breast cancer research. It also has funded cancer research programs in prostate, ovarian, brain, leukemia and lymphoma.

The grant is the latest example of collaboration between the Johns Hopkins Kimmel Cancer Center and the University of Maryland Greenebaum Cancer Center, representing Maryland's two academic medical centers. Both institutions are conducting other cancer research funded by the state's Cigarette Restitution Fund Program.

Additional grant collaborators from the Johns Hopkins Kimmel Cancer Center are Pedram Argani, assistant professor of pathology and oncology; Giovanni Parmigiani, associate professor of oncology, biostatistics and pathology; and Christopher Umbricht, assistant professor of surgery and oncology.

Among the representatives of survivor advocate groups are Lillie Shockney, Avon Foundation Breast Center at Johns Hopkins; and Nancy Armstrong, Johns Hopkins Breast Cancer Survivor Team.


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