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Senior Citizen Health & Medicine
Discovery of Stem Cells in Pancreatic Cancer May
Lead to Treatment
Pancreatic is deadliest major cancer,
with virtually no survivors
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"...we can now define
what we believe are the important cells the cells that
determine whether the cancer will come back or be cured and
target treatment directly to those cells" |
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February 1, 2007 - There is new hope in the battle
against pancreatic cancer, which most senior citizens know is the
deadliest major cancer - virtually all victims die from the disease.
Researchers today announced the discovery of stem cells in the
pancreatic tumors that fuel its growth. Researchers now can develop
drugs to target and kill these cells, which determine the life of the
cancer.
The finding by University of Michigan Comprehensive
Cancer Center researchers is the first identification of cancer stem
cells in pancreatic tumors.
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Cancer stem cells are the small number of cancer
cells that replicate to drive tumor growth. Researchers believe current
cancer treatments sometimes fail because they are not attacking the
cancer stem cells.
Over the last one to two decades we have not had a
significant improvement in the long-term survival rates with pancreatic
cancer. I believe that if we can target cancer stem cells within
pancreatic cancer we may have an avenue to really make a breakthrough in
therapy for this awful disease, says lead study author Diane Simeone,
M.D., director of the Gastrointestinal Oncology Program at the U-M
Comprehensive Cancer Center.
The cells we isolated are quite different from 99
percent of the millions of other cells in a human pancreatic tumor, and
we think that, based on some preliminary research, standard treatments
like chemotherapy and radiation may not be touching these cells, said
Simeone. If that is why pancreatic cancer is so hard to treat, a new
approach might be to design a drug that specifically targets pancreatic
cancer stem cells without interfering with normal stem cell function.
While such a drug has not been developed, ongoing
research suggests it is possible to do so, she added.
The study also advances the emerging notion that
stem cells may lie at the heart of some, if not all, cancers, Simeone
said. That theory suggests that only cells that have the properties of stemness-
that is, cells that can self-renew and differentiate into other types of
cells - are the only ones capable of producing tumors.
Researchers looked at cell markers on the surface
of tumor cells and identified a small number of cells that quickly
produced new tumors. The researchers suggest these cells are the
pancreatic cancer stem cells. Results of the study appear in the Feb. 1
issue of Cancer Research.
Tissue samples were taken from 10 patients with
pancreatic cancer. The samples were divided and implanted into mice to
grow new tumors, allowing a larger sample to be studied. The researchers
sorted the tumor cells based on whether they expressed certain antibody
markers on the cell surface, specifically CD44, CD24 and
epithelial-specific antigen, or ESA. These three markers were chosen as
a starting point based on previous work in breast cancer stem cells.
The researchers found that only 0.2 percent to 0.8
percent of the pancreatic cells expressed all three markers.
Researchers then took the sorted cells and injected
them into mice to see if new tumors formed. When 100 cells that
expressed CD44, CD24 and ESA were injected, six of the 12 mice developed
tumors. No tumors developed from the cells negative for all three
markers until 10,000 cells were injected, at which point one mouse
developed a tumor. Further, tumors that developed from these negative
cells were smaller and grew more slowly than tumors from the CD44, CD24
and ESA positive cells. The tumors that developed from these sorted
cells appeared similar to the original tumor.
In addition, the positive cells were able to
reproduce cells that expressed the three markers as well as cells
negative for those markers. This ability to self-renew and produce
different cells is a hallmark of stem cells.
The fact that we saw very consistent results in 10
different patients supports that these cells are important, says
Simeone, associate professor of surgery and of molecular and integrative
physiology at the U-M Medical School.
Stem cells have been identified in several other
cancer types, including breast, brain, central nervous system and colon
cancers, as well as leukemia. U-M researchers in 2003 were the first to
report the existence of stem cells in a solid tumor, finding them in
breast cancer.
CD44, CD24 and ESA were also found to play a role
in breast cancer stem cells. The markers that define the highly
aggressive pancreatic cancer subtype are not identically matched to
those found in aggressive breast cancer, however. The difference is in
one marker, CD24, which is negative in breast cancer and positive in
pancreatic cancer, according to Simeone.
A study published in January 2007 by U-M and
Stanford University researchers narrowed the field for head and neck
cancer stem cells, again finding that cells expressing CD44 were
involved.
Researchers suggest that a small subpopulation of
cancer cells are the critical cells in cancer growth and progression,
and the key to treating cancer is to kill these stem cells. Its a
radically different model than current treatment approaches, which are
designed to shrink the tumor by killing as many cells as possible.
Researchers suspect cancer recurs because the treatments are not killing
the stem cells.
The current model may lead to treatments limited
in their effectiveness, because we have not been targeting the most
important cells in the tumor the cancer stem cells. If we hope to cure
more cancers we will need to target and eliminate this critical type of
cancer cell, says study author Max S. Wicha, M.D., Distinguished
Professor of Oncology and director of the U-M Comprehensive Cancer
Center.
"With this finding in pancreatic cancer, we can
now define what we believe are the important cells the cells that
determine whether the cancer will come back or be cured and target
treatment directly to those cells," says Wicha, who was part of the team
that discovered stem cells in breast cancer.
About 33,700 people will be diagnosed with
pancreatic cancer this year, and about 32,300 will die from it. Five
year survival rates are a dismal 3 percent. The disease is difficult to
detect early and is often diagnosed at advanced stages. Only 10 percent
to 15 percent of patients can benefit from surgery.
Stem cells are going to radically change how we
treat cancer, Simeone says.
Editor's Notes:
In addition to Simeone and Wicha, U-M study
authors were research associate Chenwei Li; surgery resident David G.
Heidt, M.D.; Charles F. Burant, M.D., Ph.D., professor of molecular and
integrative physiology and of internal medicine; and research associate
Lanjing Zhang. Other authors were Piero Dalerba and Volkan Adsay, M.D.,
from Karmanos Cancer Institute in Detroit, and Michael F. Clarke, M.D.,
from Stanford University School of Medicine.
Funding for the study was from the Lustgarten
Foundation, the Elsa Pardee Foundation, the Michigan Life Sciences
Corridor and the American Diabetes Association.
While promising, this research is still in the
early stages of animal testing, and more research must be done before it
could benefit patients with pancreatic cancer. No therapeutic treatments
or clinical trials involving this work are available at this time. For
information on existing options for pancreatic cancer, call Cancer
AnswerLine at 800-865-1125 or visit
http://www.cancer.med.umich.edu/cancertreat/pancreatic/index.shtml.
The University of Michigan has filed for patent
protection on the relevant technologies. In the event that products come
to market, the university and the inventors of these technologies will
likely benefit financially. For information about the process by which
technologies make their way to market, and the rules that govern the
process, go to
http://www.techtransfer.umich.edu.
Reference: Cancer Research, Vol. 67, No. 3
The mission of the American Association for
Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is
the world's oldest and largest professional organization dedicated to
advancing cancer research. The membership includes more than 24,000
basic, translational, and clinical researchers; health care
professionals; and cancer survivors and advocates in the United States
and more than 70 other countries. AACR marshals the full spectrum of
expertise from the cancer community to accelerate progress in the
prevention, diagnosis and treatment of cancer through high-quality
scientific and educational programs. It funds innovative, meritorious
research grants. AACR publishes five major peer-reviewed journals:
Cancer Research; Clinical Cancer Research; Molecular Cancer
Therapeutics; Molecular Cancer Research; and Cancer Epidemiology,
Biomarkers & Prevention. Its most recent publication, CR, is a magazine
for cancer survivors, patient advocates, their families, physicians, and
scientists. It provides a forum for sharing essential, evidence-based
information and perspectives on progress in cancer research,
survivorship, and advocacy.
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