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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