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World J Stem Cells. May 26, 2023; 15(5): 438-452
Published online May 26, 2023. doi: 10.4252/wjsc.v15.i5.438
Molecular signaling in cancer stem cells of tongue squamous cell carcinoma: Therapeutic implications and challenges
Priyanka Joshi, Sanjeev Waghmare
Priyanka Joshi, Sanjeev Waghmare, Stem Cell Biology Group, Cancer Research Institute, Advanced Centre for Treatment Research and Education in Cancer, Tata Memorial Centre, Navi Mumbai 410210, India
Author contributions: Waghmare S conceptualized the review article; Waghmare S and Joshi P wrote the manuscript.
Conflict-of-interest statement: The authors have no conflicts of interest.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Sanjeev Waghmare, PhD, Senior Scientist, Stem Cell Biology Group, Cancer Research Institute, Advanced Centre for Treatment Research and Education in Cancer, Tata Memorial Centre, Sector 22, Utsav Chowk-CISF Road, Kharghar, Navi Mumbai 410210, India.
Received: December 22, 2022
Peer-review started: December 22, 2022
First decision: January 31, 2023
Revised: February 21, 2023
Accepted: April 7, 2023
Article in press: April 7, 2023
Published online: May 26, 2023

Head and neck squamous cell carcinoma is the seventh most common cancer worldwide with high mortality rates. Amongst oral cavity cancers, tongue carcinoma is a very common and aggressive oral cavity carcinoma. Despite the implementation of a multimodality treatment regime including surgical intervention, chemo-radiation as well as targeted therapy, tongue carcinoma shows a poor overall 5-year survival pattern, which is attributed to therapy resistance and recurrence of the disease. The presence of a rare population, i.e., cancer stem cells (CSCs) within the tumor, are involved in therapy resistance, recurrence, and distant metastasis that results in poor survival patterns. Therapeutic agents targeting CSCs have been in clinical trials, although they are unable to reach into therapy stage which is due to their failure in trials. A more detailed understanding of the CSCs is essential for identifying efficient targets. Molecular signaling pathways, which are differentially regulated in the CSCs, are one of the promising targets to manipulate the CSCs that would provide an improved outcome. In this review, we summarize the current understanding of molecular signaling associated with the maintenance and regulation of CSCs in tongue squamous cell carcinoma in order to emphasize the need of the hour to get a deeper understanding to unravel novel targets.

Keywords: Head and neck squamous cell carcinoma, Cancer stem cells, Signaling, Tongue squamous cell carcinoma

Core Tip: Tongue squamous cell carcinoma is one of the most common and aggressive oral cavity carcinomas, particularly among the Indian population. Despite various treatment strategies employed, the survival rates of the patients remain poor. A rare population i.e., cancer stem cells (CSCs), plays an important role in resistance, recurrence as well as metastasis which are factors responsible for the poor survival outcome. In this review, we discuss the recent findings regarding cell signaling pathways and markers associated with the CSCs and the need to gain a deeper understanding on the properties of the CSCs.