Preliminary data from one of the first clinical trials
to test a stem cell-targeting drug in cancer
patients shows that while the drug did not prolong
survival, its suppressing effect on patients' stem
cells was impressive enough to send investigators looking
for a better drug to try.
As an emerging field of study in cancer research, stem
cells are believed to sprout cancer much
like the hidden roots of weeds that elude efforts to get
rid of them.
Rituximab, a drug currently approved to treat B-cell
lymphomas, and a common chemotherapy
agent, cyclophosphamide, were given to 21 patients whose
multiple myeloma, a cancer of the bone
marrow, had relapsed or was defined as high-risk first
remission. A previous study using the drug
alone in multiple myeloma patients suggested that the
disease in some participants progressed more
slowly.
During the study, the Johns Hopkins team examined the
stem cells under the microscope. "We
found cancer stem cells coated with rituximab, but the drug
wasn't killing them," said Carol Ann Huff,
assistant professor of
oncology. "We think the idea is correct, but the drug
itself wasn't the right
one." Rituximab is sold under the trade name Rituxan.
Huff and her team believe that multiple therapies are
required to kill cancer: one to get rid of
the bulk of the tumor, like mowing the lawn, and another to
hit the root of the cancer, its stem cells.
William Matsui, assistant professor of medicine at the
Johns Hopkins Kimmel Cancer Center,
said, "We think one reason that cancer comes back is
because stem cells, which are resistant to
chemotherapy, repopulate the body with new cancer
cells."
The team's test of the rituximab-cyclophosphamide
combo showed up to a 1000-fold reduction
in cancer stem cells during the initial treatment.
However, stem cell quantities eventually crept back up
and led to a progression of disease.
Investigators were able to predict when patients' disease
would recur by tracking the number of stem
cells they had. The average advance notice was two
months.
Since the study began in early 2005, four patients
have died from their disease, three remain
progression-free, and the rest have disease that has
progressed.
Matsui and Huff are currently testing drugs that block
an enzyme called telomerase, which may
give cancer stem cells longevity, and other drugs that
block a stem cell-signaling pathway called
hedgehog. Other promising therapies, according to the
scientists, include a combination of the growth
factors interleukin-6 and interferon-alpha, which may
prematurely age stem cells.
The scientists presented their findings April 13 at
the American Association for Cancer
Research Annual Meeting in San Diego, Calif.
Funding for the study was provided by the National
Cancer Institute, American Society of
Clinical Oncology, Commonwealth Foundation and Genentech.
In addition to Matsui and Huff, Johns
Hopkins scientists participating in the study were Q. Wang,
K. Rogers, M. Jung, Javier Bolanos-Meade,
Ivan Borrello and Richard Jones.
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