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Oral Oncol. 2016 Nov;62:122-135. doi: 10.1016/j.oraloncology.2016.10.008. Epub 2016 Oct 25.

Implications of cancer stem cells in developing therapeutic resistance in oral cancer.

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Department of Life Science, National Institute of Technology, Rourkela, Odisha, India.
Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Denver, Aurora, CO, United States; University of Colorado Cancer Center, University of Colorado Denver, Aurora, CO, United States. Electronic address:
Department of Life Science, National Institute of Technology, Rourkela, Odisha, India. Electronic address:


Conventional therapeutics are often frequented with recurrences, refraction and regimen resistance in oral cavity cancers which are predominantly manifested by cancer stem cells (CSCs). During oncoevolution, cancer cells may undergo structural and functional reprogramming wherein they evolve as highly tolerant CSC phenotypes with greater survival advantages. The CSCs possess inherent and exclusive properties including self-renewal, hierarchical differentiation, and tumorigenicity that serve as the basis of chemo-radio-resistance in oral cancer. However, the key mechanisms underlying the CSC-mediated therapy resistance need to be further elucidated. A spectrum of dysfunctional cellular pathways including the developmental signaling, apoptosis, autophagy, cell cycle regulation, DNA damage responses and epigenetic regulations protect the CSCs from conventional therapies. Moreover, tumor niche shelters CSCs and creates an immunosuppressive environment favoring the survival of CSCs. Maintenance of lower redox status, epithelial-to-mesenchymal transition (EMT), metabolic reprogramming and altered drug responses are the accessory features that aid in the process of chemo-radio-resistance in oral CSCs. This review deals with the functional and molecular basis of cancer cell pluripotency-associated resistance highlighting the abrupt fundamental cellular processes; targeting these events may hold a great promise in the successful treatment of oral cancer.


Cancer stem cells; Oral cancer; Therapy resistance; Tumorigenicity

[Indexed for MEDLINE]

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