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The cancer stem-cell hypothesis: its emerging role in lung cancer biology and its relevance for future therapy.
MedLine Citation:
PMID:  23154562     Owner:  NLM     Status:  In-Data-Review    
The cancer stem-cell (CSC) hypothesis suggests that there is a small subset of cancer cells that are responsible for tumor initiation and growth, possessing properties such as indefinite self-renewal, slow replication, intrinsic resistance to chemotherapy and radiotherapy, and an ability to give rise to differentiated progeny. Through the use of xenotransplantation assays, putative CSCs have been identified in many cancers, often identified by markers usually expressed in normal stem cells. This is also the case in lung cancer, and the accumulated data on side population cells, CD133, CD166, CD44 and ALDH1 are beginning to clarify the true phenotype of the lung cancer stem cell. Furthermore, it is now clear that many of the pathways of normal stem cells, which guide cellular proliferation, differentiation, and apoptosis are also prominent in CSCs; the Hedgehog (Hh), Notch, and Wnt signaling pathways being notable examples. The CSC hypothesis suggests that there is a small reservoir of cells within the tumor, which are resistant to many standard therapies, and can give rise to new tumors in the form of metastases or relapses after apparent tumor regression. Therapeutic interventions that target CSC pathways are still in their infancy and clinical data of their efficacy remain limited. However Smoothened inhibitors, gamma-secretase inhibitors, anti-DLL4 antagonists, Wnt antagonists, and CBP/β-catenin inhibitors have all shown promising anticancer effects in early studies. The evidence to support the emerging picture of a lung cancer CSC phenotype and the development of novel therapeutic strategies to target CSCs are described in this review.
John D O'Flaherty; Martin Barr; Dean Fennell; Derek Richard; John Reynolds; John O'Leary; Kenneth O'Byrne
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer     Volume:  7     ISSN:  1556-1380     ISO Abbreviation:  J Thorac Oncol     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-11-16     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101274235     Medline TA:  J Thorac Oncol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1880-90     Citation Subset:  IM    
*Thoracic Oncology Research Group, Institute of Molecular Medicine, St, James's Hospital, Dublin, Ireland; †Centre for Cancer Research & Cell Biology, School of Medicine, Dentistry & Biomedical Science, Queen's University, Belfast, Ireland; ‡Faculty of Science and Technology, CELS Portfolio (Chemical, Earth & Life Sciences), Cell and Molecular Biosciences, Queensland University of Technology, Brisbane, Australia; and Departments of §Surgery, and ‖Histopathology, Trinity College, Dublin, Ireland.
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