Cancer stem cells, the ultimate targets in cancer therapy
Ahmed Shabbir,1 Tuba Esfandyari,2 Faris Farassati1,3,4
1Midwest Biomedical Research Foundation, Kansas City Veterans Affairs Medical Center, 2Department of Medicine, School of Medicine, The University of Kansas, 3Saint Luke’s Cancer Institute, 4Saint Luke’s Marion Bloch Neuroscience Institute, Saint Luke’s Health System, Kansas City, MO, USA
The concept of cancer stem cells (CSCs) is currently of significant interest due to its important implications in our understanding of the tumor biology as well as development of novel cancer therapeutics. Tumors, in resemblance to normal organs, contain pluripotential cells that can generate their own kind as well as cells that can further differentiate. CSCs are thought to be highly resistant to the cytotoxic effects of conventional cancer therapy regimens,1 which leads to the rise of a refractory status in tumors.1,2 Therefore, CSCs can be considered as the main drivers of tumor integrity and function. This resembles the role of normal stem cells in tissue and organ development. Therapeutic assaults that eliminate differentiated cancer cells while leaving CSCs, therefore, are doomed to fail due to the resistance of CSCs and their ability to repopulate the tumor.3 This phenomenon is indeed observed in the clinic routinely. Clinical response to a chemotherapy regimen is reduced over time as the tumor enters a refractory stage induced by enrichment of CSCs in the tumor cell population. This is even observed in cells cultured from a patient at early stage of the disease, such as in colorectal cancer (SW480, ATCC CCL-228), and recurrence of the malignancy results in a wide-spread metastasis (SW620, ATCC CCL-227). The SW260 shows a significantly higher percentage of cells positive for CD133, a marker for CSCs (data from our team). Methods for the detection of CSCs include surface markers such as CD24, CD34, CD44, CD44, CD90, CD133, ABCB5, and EpCAM that have been shown to indicate CSC subpopulations in a range of malignancies.4 Additionally, functional tests, such as detection of side population phenotype by Hoechst 33342 exclusion, the ability to grow as floating spheres in serum-free medium, and ALDH activity, have also been utilized to detect and isolate CSCs.
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