Journal
GENES & DEVELOPMENT
Volume 29, Issue 12, Pages 1203-1217Publisher
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.261982.115
Keywords
brain tumor; cancer stem cell; glioblastoma; glioma; stem cell; tumor-initiating cell
Categories
Funding
- National Institutes of Health [CA154130, CA171652, CA169117, NS087913, NS089272, CA157948, CA191263, NS083629]
- Sontag Foundation
- Research Programs Committees of Cleveland Clinic
- James S. McDonnell Foundation
- Canadian Institutes of Health Research Banting Fellowship
- Lerner Research Institute
- Case Comprehensive Cancer Center
- Voices Against Brain Cancer
- Blast GBM
- Ohio Cancer Research Associates
- Research Scholar Award from the American Cancer Society
- V Scholar Award from the V Foundation for Cancer Research
- American Cancer Society [IRG-91-022-18]
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Tissues with defined cellular hierarchies in development and homeostasis give rise to tumors with cellular hierarchies, suggesting that tumors recapitulate specific tissues and mimic their origins. Glioblastoma (GBM) is the most prevalent and malignant primary brain tumor and contains self-renewing, tumorigenic cancer stem cells (CSCs) that contribute to tumor initiation and therapeutic resistance. As normal stem and progenitor cells participate in tissue development and repair, these developmental programs re-emerge in CSCs to support the development and progressive growth of tumors. Elucidation of the molecular mechanisms that govern CSCs has informed the development of novel targeted therapeutics for GBM and other brain cancers. CSCs are not self-autonomous units; rather, they function within an ecological system, both actively remodeling the microenvironment and receiving critical maintenance cues from their niches. To fulfill the future goal of developing novel therapies to collapse CSC dynamics, drawing parallels to other normal and pathological states that are highly interactive with their microenvironments and that use developmental signaling pathways will be beneficial.
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