Page 46 - Read Online

Page 16 of 23 ALHulais et al. J Cancer Metastasis Treat 2019;5:3 I http://dx.doi.org/10.20517/2394-4722.2018.71

and treatment. It should be possible to identify and thereby improve the development of drugs used as
biological modifiers to eliminate the CSC populations by relying on the selective biomarkers Cripto-1,
ABCG2, LGR5 and CD271 to aid in the analysis of CSC drug sensitivity. From the range of evidence
provided, it is apparent that such CSC markers are expressed in common across many cancer types and with
ESCs. In this manner, the CSC biomarkers can be used to separate enriched CSC populations from the other
non-tumorigenic cells and normal stem cells using cell-sorting technology to then identify those drugs with
greater potential for specifically and selectively targeting the CSCs by activating their cell death programs.
One such drug is celecoxib, with one of its properties being an inhibitor of the COX-2/PGE production by
CSCs, otherwise required for promoting greater LGR5 expression and WNT signalling to enhance CSC
proliferation.

Cancer treatments have repeatedly failed due to their inability to target and kill the CSCs because these cells
are highly resistant to commonly used chemotherapies, having greater survival and metastatic properties.
The CSCs can remain dormant, only to then become reactivated, with their capacity for self-renewal and
extensive proliferation, metastasis and differentiation giving rise to recurrent tumors, even after extended
periods post-treatment. Therefore, it will be essential to be able to identify the CSCs, isolate and study their
characteristics in greater detail in order to develop better drug treatments, such as celecoxib, and where the
evidence is compelling that such drugs can then either promote or induce the death of the CSCs, both in the
circulation and in tumor niches.

DECLARATIONS
Authors’ contributions
Both authors contributed equally to the writing, construction and editing of the manuscript as well as
drawing of the figures.

Availability of data and materials
Not applicable.

Financial support and sponsorship
ALHulais RA was supported by the Higher Education of Saudi Arabia (King Abdullah Scholarship) for her
PhD program.

Conflicts of interest
Both authors declared that there are no conflicts of interest.

Ethical approval and consent to participate
Not applicable.

Consent for publication
Not applicable.

Copyright
© The Author(s) 2019.

REFERENCES
1. Kozovska Z, Gabrisova V, Kucerova L. Colon cancer: cancer stem cells markers, drug resistance and treatment. Biomed Pharmacother
2014;68:911-6.
2. Shimokawa M, Ohta Y, Nishikori S, Matano M, Takano A, et al. Visualization and targeting of LGR5+ human colon cancer stem cells.
Nature 2017;545:187-92.