The stem cell code in oral epithelial tumorigenesis: ‘The cancer stem cell shift hypothesis’

Tumors of the oral cavity provide an ideal model to study various stages of epithelial tumor progression. A group of cancer cells termed cancer stem cells (CSCs) eludes therapy, persists and initiates recurrence augmenting malignant spread of the disease. Hitherto, accurate identification and separation of such minimal residual cells have proven futile due to lack of identifiable traits to single out these cells from the heterogeneous tumor bulk. In this review we have compiled comprehensive evidence from comparative phenotypic and genotypic studies on normal oral mucosa as well as tumors of different grades to elucidate that differential expression patterns of putative stem cells markers may identify ‘minimal residual disease’ in oral squamous cell carcinoma. We propose the “cancer stem cell shift hypothesis” to explain the exact identity and switch-over, tumor-promoting mechanisms adapted by putative CSCs with correlation to tumor staging.