The cancer stem-cell hypothesis : its emerging role in lung cancer biology and its relevance for future therapy
O’Flaherty, John D., Barr, Martin, Fennell, Dean, Richard, Derek, Reynolds, John, O’Leary, John, & O’Byrne, Kenneth J. (2012) The cancer stem-cell hypothesis : its emerging role in lung cancer biology and its relevance for future therapy. Journal of Thoracic Oncology, 7(12), pp. 1880-1890.
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.
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|Item Type:||Journal Article|
|Keywords:||Cancer Stem Cell, Non-small cell lung cancer, Small cell lung cancer, Tumour-initiating cell, Embryonic stem cell, Hedgehog, Notch, Wnt, Side population, Aldehyde dehydrogenase, CD133, CD44, CD166, Beta-catenin, KRAS|
|Subjects:||Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > ONCOLOGY AND CARCINOGENESIS (111200) > Cancer Cell Biology (111201)
Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > ONCOLOGY AND CARCINOGENESIS (111200) > Cancer Genetics (111203)
|Divisions:||Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
|Copyright Owner:||Copyright 2012 International Association for the Study of Lung Cancer|
|Deposited On:||02 Jan 2013 06:36|
|Last Modified:||12 Dec 2013 00:51|
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