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Cancer Stem Cells—Perspectives on
Current Status and Future Directions: AACR Workshop on Cancer Stem
Cells
Michael F. Clarke1,
John E. Dick2, Peter
B. Dirks3, Connie
J. Eaves4, Catriona
H.M. Jamieson5, D.
Leanne Jones6, Jane
Visvader7, Irving
L. Weissman8 and Geoffrey
M. Wahl6
1Stanford University
School of Medicine, Stanford, California; 2University
Health Network; 3University of Toronto Hospital for Sick
Children, Toronto, Ontario, Canada; 4Terry Fox Laboratory
BC Cancer Research Center, Vancouver, British Columbia, Canada; 5Moores
University of California San Diego Cancer Center; 6The Salk
Institute for Biological Studies, La Jolla, California; 7Walter
and Eliza Hall Institute, Parkville, Victoria, Australia; and 8Stanford
University Medical Center, Palo Alto, California -- Requests for
reprints: Geoffrey M. Wahl, The Salk Institute for Biological Studies,
10010 North Torrey Pines Road, La Jolla, CA 92037. Phone:
858-453-4100, ext. 1587; Fax: 858-457-2762; E-mail: wahl@salk.edu
. -- Received 8/23/06. Accepted 8/23/06. -- Note: The AACR Cancer Stem
Cells Workshop was held on February 2-4, 2006 in Lansdowne,
Virginia.
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A workshop was convened by the AACR to
discuss the rapidly emerging cancer stem cell model for
tumor development and progression.
The meeting participants were charged with
evaluating data suggesting that cancers develop from a
small subset of cells with self-renewal properties
analogous to organ stem cells.
Indeed, one critical question
contemplated at the Workshop was whether tumors derive from
organ stem cells that retain self-renewal properties but acquire
epigenetic and genetic changes required for tumorigenicity or
whether tumor stem cells are proliferative progenitors that acquire
self-renewal capacity.
Of course, both mechanisms may occur
and may depend on the organ site.
Either mechanism is different
from the widely held notion that most cells in a tumor should
be competent for tumor formation.
If the cancer stem cell model
is correct and if such cells retain the hallmarks of some
tissue stem cells in being rare and entering the cell cycle
infrequently, they could constitute a population that is
intrinsically resistant to current therapies designed to kill
cycling cells.
The participants critically discussed the
need for a precise definition of cancer stem cells, the
requirement for new markers and more rapid and tractable in
vitro and in vivo assays, and the need to
develop drug screening strategies to selectively target
cancer stem cells to generate therapeutics for this
subpopulation of cells that could be resistant to classic treatments
while possessing potent tumor-forming capacity.
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