Molecular signaling in cancer stem cells of tongue squamous cell carcinoma: Therapeutic implications and challenges

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.

Key Words: 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.