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ALHulais et al. J Cancer Metastasis Treat 2019;5:3 I http://dx.doi.org/10.20517/2394-4722.2018.71 Page 3 of 23

A

B

Figure 1. A: Targeting cancer stem cells: current treatments with conventional chemotherapy are not highly efficient against the cancer
stem cells (CSCs) residing in tumors which resist chemotherapy or radiation and post-treatment will undergo self-renewal, differentiation
and tumor regrowth or metastasize causing relapse and formation of additional tumors. However, drugs targeting the CSC population
(such as celecoxib) can be used to eliminate the CSCs, either by direct cytotoxic effects or by sensitizing these tumor cells to other
chemotherapy, resulting in the clonal extinction of the entire tumor cell population; B: The treatment concept of targeting CSCs (also
known as the “Dandelion hypothesis”) by analogy proposes that by eliminating the roots (CSC population), the plant (tumor) can not
become re-established whereas cutting the flowering stalks, stem or branches away will allow regrowth [8]

their elimination. These findings should then be applicable to other CSC types. Historically, CSCs were
extracted from solid tumors and partially purified as a poorly or negatively staining side population (SP)
by flow cytometry, so-called because of their hallmark characteristic to exclude the nuclear DNA staining,
fluorescent Hoechst series of dyes, such that CSCs could be separated from the bulk of other tumor cells
[14]
that were highly positive for the nuclear DNA stain . These poorly stained “SP” CSCs often showed much
greater stem-like self-renewal and increased tumor-initiating capability and were responsible for tumor
[14]
recurrence because they were more resistant to many forms of chemotherapy .
Other methods have also been used to enrich for CSCs, including growing tumor cells suspended in serum-
TM
free defined media or above agarose to form spheres or spheroids or by selective uptake of the Aldefluor
[15]
stem cell stains because CSCs show greater expression of aldehyde dehydrogenase 1 . The use of such
methods for the identification and definition of CSCs has been complicated by observations that in the