The cancer stem cell hypothesis applied to oral carcinoma

It has been proposed that the development of tumors is based exclusively on the activity of cancer stem cells (CSCs) leading to a new model of carcinogenesis, the CSC hypothesis, in opposition to the conventional model of clonal evolution. The new model may help to explain the high mortality of oral cancer, unchanged over the past decades, the low response to treatment and the tendency of oral squamous cell carcinoma (OSCC) patients to develop multiple tumors. However, a more profound understanding of the molecular pathways involved in maintaining the stem cell (SC) state and of their alterations is required to elucidate the mechanisms underlying the development of tumors and metastatic spread, but research into SC biopathology is hampered by the lack of specific markers for identifying SCs and CSCs in tissues and for establishing topographic relationships with their lineage. We review current knowledge on stem cells in relation to oral cancer, including their possible origins, focusing on the CSC hypothesis of oral tumorigenesis and attempts being made to identify oral stem cells.