Survival of the fittest: Cancer stem cells in therapeutic resistance and angiogenesis

被引:562
作者
Eyler, Christine E.
Rich, Jeremy N. [1 ]
机构
[1] Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Prseton Robert Tisch Brain Tumor Ctr, Durham, NC 27710 USA
关键词
D O I
10.1200/JCO.2007.15.1829
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
In an increasing number of cancers, tumor populations called cancer stem cells (CSCs), or tumor-initiating cells, have been defined in functional assays of self-renewal and tumor initiation. Moreover, recent work in several different cancers has suggested the CSC population as a source of chemotherapy and radiation-therapy resistance within tumors. Work in glioblastoma and breast cancers supports the idea that CSCs may possess innate resistance mechanisms against radiation- and chemotherapy-induced cancer cell death, allowing them to survive and initiate tumor recurrence. Several resistance mechanisms have been proposed, including amplified checkpoint activation and DNA damage repair as well as increased Wnt/beta-catenin and Notch signaling. Novel targeted therapies against the DNA damage checkpoint or stem-cell maintenance pathways may sensitize CSCs to radiation or other therapies. Another important category of cancer therapies are antiangiogenic and vascular targeting agents, which are also becoming integrated in the treatment paradigm of an increasing number of cancers. Recent results from our laboratory and others support a role for CSCs in the angiogenic drive as well as the mechanism of antiangiogenic agents. Identifying and targeting the molecular mechanisms responsible for CSC therapeutic resistance may improve the efficacy of current cancer therapies.
引用
收藏
页码:2839 / 2845
页数:7
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