Relevance of cancer initiating/stem cells in carcinogenesis and therapy resistance in oral cancer

Oral squamous cell carcinoma (OSCC) acquires the top most position among the other malignancies and patients die with this disease complication within 5 years. One of the causes behind this scenario is the identified sub-population in heterogeneous tumor mass that are purported as cancer stem cells (CSCs) or tumor-initiating cells (TICs). Oral CSCs populations show upregulation of the stem cell related genes Oct-4, Nanog, Nestin, CK19, BMI-1, CD117 (c-kit), CD44 and CD133 with sunken expression of involucrin and CK13. This small proportion of tumor cells can sustain tumor growth, proliferation, invasion and distant metastasis playing a pivotal role in relapse of oral cancer. Unanimous risk factors include prevalent use of cigarette smoking, tobacco chewing with less explored HPV infection play an important role in origin of CSCs. Moreover, highly apoptotic resistant oral CSCs show enhanced protective autophagy for survival. Several studies report them to be more chemo and radiation resistant than non-stem cell population implicating the failure of the present cancer therapy. This resistance associated with normal stem cell protective mechanisms including increased expression of drug efflux pumps, alteration in program cell death, cell cycle, and DNA repair mechanisms. Notably, CSCs appear to play a major role in tumor recurrence and metastatic spread, common causes of the high morbidity and ultimately the death of the majority of patients with oral cancer. In this review we would like to highlight the intricate crosstalk of the cancer initiating/stem cells involved in carcinogenesis and potential hurdle to oral cancer therapy.