Blocking Growth Protein Kills Prostate Cancer Cells, Inhibits Tumor Growth, Jefferson Scientists Find
Researchers
at Jefferson’s Kimmel Cancer Center in Philadelphia have shown that
they can effectively kill prostate cancer cells in both the laboratory
and in experimental animal models by blocking a signaling protein that
is key to the cancer’s growth. The work proves that the protein, Stat5,
is both vital to prostate cancer cell maintenance and that it is a
viable target for drug therapy.
The
scientists, led by Marja Nevalainen, M.D., Ph.D., associate professor
of Cancer Biology at Jefferson Medical College of Thomas Jefferson
University, wanted to prove that Stat5 was indeed necessary for
prostate cancer cells to be viable. They blocked the protein’s
expression and function in several ways, including siRNA inhibition,
antisense inhibition and adenoviral gene delivery of an inhibitory form
of Stat5. All of these techniques killed the prostate cancer cells in
cell culture. The researchers also showed when they transplanted such
cancerous tissue into mice and blocked Stat5 expression, prostate
tumors failed to grow.
“This
provides the proof of principle that Stat5 is a therapeutic target
protein for prostate cancer, and may be specifically useful for
advanced prostate cancer, where there are no effective therapies,” Dr.
Nevalainen says. “These results are very reproducible.” She and her
team report their findings March 1, 2008 in the journal Clinical Cancer Research.
Hormone
resistant prostate cancer is especially dangerous. Men with primary
prostate cancer usually have either surgery or radiation, whereas
subsequent disease is frequently treated by hormone therapy. But if the
cancer recurs again, years later, it can be more aggressive and
typically fails to respond to hormone treatment, often leaving few
treatment options.
The
findings, Dr. Nevalainen notes, are particularly relevant because her
team worked with urologists to get human prostate cancer tissue
specimens from surgeries, putting them into cell tissue cultures. That
way, she says, the hypothesis could be tested in real human prostate
cancer tissue specimens.
While
she and her team continue to work on establishing Stat5 as a
therapeutic target for hormone-resistant prostate cancer, they are also
testing whether or not blocking Stat5 can make prostate cancer cells
more sensitive to other treatments, such as radiation and chemotherapy.
Another next step in the work, Dr. Nevalainen says, is to find
pharmacological agents that inhibit the protein.
In work reported recently in Cancer Research,
Dr. Nevalainen and her co-workers showed that Stat5 is turned on in
nearly all recurrent prostate cancers that are resistant to hormone
therapy. In addition, the researchers also showed that the convergence
of Stat5 and androgen receptor could be responsible for making such
prostate cancers especially dangerous.
Media Only Contact:
Steve Benowitz
Thomas Jefferson University Hospital
Phone: (215) 955-6300
Published: 2/28/2008