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Cancer stem cells in glioblastoma — molecular
signaling and therapeutic targeting |
| Zhi Huang,Lin Cheng,Olga A. Guryanova,Qiulian Wu,Shideng Bao, |
| Department of Stem Cell
Biology and Regenerative Medicine, Lerner Research Institute, Cleveland
Clinic, Cleveland, OH 44195, USA; |
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Abstract Glioblastomas (GBMs) are highly lethal primary brain tumors. Despite current therapeutic advances in other solid cancers, the treatment of these malignant gliomas remains essentially palliative. GBMs are extremely resistant to conventional radiation and chemotherapies. We and others have demonstrated that a highly tumorigenic subpopulation of cancer cells called GBM stem cells (GSCs) promotes therapeutic resistance. We also found that GSCs stimulate tumor angiogenesis by expressing elevated levels of VEGF and contribute to tumor growth, which has been translated into a useful therapeutic strategy in the treatment of recurrent or progressive GBMs. Furthermore, stem cell-like cancer cells (cancer stem cells) have been shown to promote metastasis. Although GBMs rarely metastasize beyond the central nervous system, these highly infiltrative cancers often invade into normal brain tissues preventing surgical resection, and GSCs display an aggressive invasive phenotype. These studies suggest that targeting GSCs may effectively reduce tumor recurrence and significantly improve GBM treatment. Recent studies indicate that cancer stem cells share core signaling pathways with normal somatic or embryonic stem cells, but also display critical distinctions that provide important clues into useful therapeutic targets. In this review, we summarize the current understanding and advances in glioma stem cell research, and discuss potential targeting strategies for future development of anti-GSC therapies.
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| Keywords
cancer stem cell
glioblastoma
therapeutic resistance
molecular targeting
tumor angiogenesis
hypoxia response
stem cell niche
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Issue Date: 01 July 2010
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