title: Cancer stem cells in glioblastoma--molecular signaling and therapeutic targeting.
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.
authors.affiliation: Department of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Huang
authors.forename: Lin
authors.initials: L
authors.lastname: Cheng
authors.forename: Olga A
authors.initials: OA
authors.lastname: Guryanova
authors.forename: Qiulian
authors.initials: Q
authors.lastname: Wu
authors.forename: Shideng
authors.initials: S
authors.lastname: Bao
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D002454:Cell Differentiation; D015687:Cell Hypoxia; D019008:Drug Resistance, Neoplasm; D005786:Gene Expression Regulation; D005909:Glioblastoma / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D006801:Humans; D035683:MicroRNAs / Q000502:physiology; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D009389:Neovascularization, Pathologic; D011836:Radiation Tolerance; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs; D014157:Transcription Factors