RESEARCH STUDY MAPS FORMATION PROCESS OF CERTAIN TYPE OF BREAST CANCER
Research Yields Array of Possible Drug Targets
A slow-motion movie of the changes inside a breast cell as it
becomes a particularly stubborn type of cancer cell would
show a process very much like that depicted for the first time in
a new study by researchers at Dana-Farber.
The investigators, led by Debajit Biswas, D.Sc., in the
laboratory of Arthur Pardee, Ph.D., of Dana-Farber's Cancer
Biology department, have charted the chain of events by which
breast cancer cells known as estrogen receptor-negative (or
ER-negative) cells are formed. Because such cells do not need
the female hormone estrogen to grow and proliferate,
conventional drugs like tamoxifen that block estrogen from
acting on breast cells are generally ineffective against
ER-negative tumors. About 30 percent of all breast cancers
are ER-negative.
"The discovery of the steps involved in the creation of
ER-negative breast cancer cells means scientists now have an
array of targets for drugs that may be able to stop the process
in its tracks, providing the first specific therapy for patients with
ER-negative breast tumors," Biswas says.
Thus far, the studies have been conducted in laboratory
samples of cells only.
The study, published in the most recent issue (July 18) of the
Proceedings of the National Academy of Sciences, focuses on
what happens after ER-negative cells have been stimulated to
grow.
The on-off switch for growth in ER-negative cells is a
"receptor" on the cell surface. When the receptor meets a
substance called epidermal growth factor (EGF), it signals the
cell to begin dividing uncontrollably.
In the new laboratory study, Biswas and his colleagues map
out some of the key stages in the process of ER-negative cells'
becoming cancerous (see Figure 1). One involves a protein
complex called nuclear factor kappa B (NF-kB), which is
activated when EGF docks at the cell. In its active form,
NF-kB serves as an "ignition switch" for cell division.
The activation of NF-kB by EGF is itself a complex process,
involving several stages and at least three different enzyme
systems. Biswas' team has shown those stages in detail - and,
just as importantly - shown that one of them can be blocked by
a compound called Go6976. The compound essentially
short-circuits the growth signals within cancerous ER-negative
cells and causes them to die.
Biswas and his associates have been carrying out this study
with support from the Massachusetts Department of Public
Health Breast Cancer Research Program.
Dana-Farber researchers are currently searching for other
substances that can hinder the over-proliferation of
ER-negative cells. The next step will be to test Go6976 and
other compounds either singly or in combinations in laboratory
animals to see if they're safe and effective against ER-negative
breast tumors grown in these animals. Compounds that
succeed in those tests will be candidates for study in human
patients.
Dana-Farber Cancer Institute (www.dana-farber.net) is a
principle teaching hospital of Harvard Medical School and
among the leading cancer research and care centers in the
United States. It is the only center in New England to be both a
NCI Comprehensive Cancer Center and a NIH Center for
Aids Research.
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