Journal of the National Cancer Institute Advance Access originally published online on September 25, 2007
JNCI Journal of the National Cancer Institute 2007 99(19):1435-1440; doi:10.1093/jnci/djm136
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© The Author 2007. Published by Oxford University Press.
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COMMENTARY |
"Destemming" Cancer Stem Cells
Affiliations of authors: Ontario Cancer Institute/Princess Margaret Hospital, University Health Network, and Department of Medical Biophysics, University of Toronto, Toronto, Canada (RPH); Laboratory of Cancer and Stem Cell Biology, Department of Genetics, Microbiology and Anthropology, University of Parma, Parma, Italy (RP); Division for Experimental Oncology 2, The National Cancer Institute CRO-IRCCS, Aviano, Italy (RP)
Correspondence to: Richard P. Hill, PhD, Ontario Cancer Institute/Princess Margaret Hospital, University Health Network, and Department of Medical Biophysics, University of Toronto, 610 University Ave, Toronto, Canada M5G2M9 (e-mail: hill{at}uhnres.utoronto.ca).
Cancer stem cells have been variously defined as cells within a cancer that have the exclusive ability to self-renew and to differentiate into the heterogeneous lineages of cancer cells that comprise the tumor. Interest in cancer stem cells is currently high, arising from recent reports identifying cell surface markers that can be used to sort such cells from primary human tumors. However, use of the term cancer stem cell may be misleading. A better term might be cancer-initiating cells because it remains to be demonstrated that cancer stem cells have the properties that define normal stem cells, including multipotency and the ability to undergo asymmetric and symmetric divisions. Many properties of cancer stem cells remain unclear, particularly the stability of their phenotype. These uncertainties must be considered in the development and testing of compounds targeted against putative cancer stem cells. Tumors apparently contain very few cancer stem cells, so that when tests of compounds targeted to such cells are designed, short-term response trials may not be informative and long-term trials must be planned, particularly if the drugs could also kill normal stem cells.
National Cancer Institute of Canada with funds raised by the Terry Fox Run (15004 to R. P. H.); Canadian Institutes of Health Research (144089 to R. P. H.); National Institutes of Health/National Institute of Allergy and Infectious Diseases (U19AI067734, U19AI067733 to R. P. H.); Associazione Italiana per la Ricerca sul Cancro (to R. P.); Italian Ministry of Health (RF04 to R. P.); University of Parma (to R. P.); National Cancer Institute, Aviano (to R. P.).
The authors acknowledge useful discussions with Dr John Dick. The authors had full responsibility for the writing of the manuscript, its submission for publication, the analysis, and interpretations presented.
Manuscript received January 22, 2007; revised July 17, 2007; accepted August 6, 2007.
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J Natl Cancer Inst 2007 99: 1421.
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