Hill Richard P, Perris Roberto
Ontario Cancer Institute/Princess Margaret Hospital, University Health Network, and Department of Medical Biophysics, University of Toronto, 610 University Ave, Toronto, Canada M5G2M9.
J Natl Cancer Inst. 2007 Oct 3;99(19):1435-40. doi: 10.1093/jnci/djm136. Epub 2007 Sep 25.
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.
癌症干细胞被以多种方式定义为癌症组织中具有自我更新的独特能力,并能分化为构成肿瘤的异质性癌细胞谱系的细胞。目前人们对癌症干细胞的兴趣浓厚,这源于最近有报道称发现了可用于从原发性人类肿瘤中筛选此类细胞的细胞表面标志物。然而,使用“癌症干细胞”这一术语可能会产生误导。一个更好的术语或许是“癌症起始细胞”,因为仍有待证明癌症干细胞具备定义正常干细胞的特性,包括多能性以及进行不对称和对称分裂的能力。癌症干细胞的许多特性仍不明确,尤其是其表型的稳定性。在开发和测试针对假定的癌症干细胞的化合物时,必须考虑这些不确定性。肿瘤中显然只含有极少数的癌症干细胞,因此在设计针对此类细胞的化合物测试时,短期反应试验可能无法提供有用信息,必须规划长期试验,特别是如果药物也可能杀死正常干细胞的话。