Cancer stem cells in head and neck squamous cell carcinoma: a review of current knowledge and future applications.

Head and neck squamous cell carcinoma (HNSCC) is a major cause of morbidity and mortality, and the alleviation thereof requires greater understanding of the pathobiologic behavior of HNSCC. Although the existence of cancer stem cells (CSCs) in most solid tumors has not been formally proven, application of the CSC concept has certainly enhanced understanding of HNSCC heterogeneity and progression. Recent data support the role of ALDH1(+) CD44(+) CSC in HNSCC, since the implantation of a few ALDH1(+) CD44(+) cells consistently gives rise to tumors that can be serially passaged in vivo. In addition to CSC biomarkers, recent explorations of CSC signaling pathways, gene expression, and localization in HNSCC carry significant clinical and therapeutic implications. Identification and characterization of CSC populations that regulate HNSCC growth, metastasis, and treatment resistance will facilitate development of novel diagnostic, therapeutic, and prognostic strategies. Furthermore, advances in multimodal imaging and nanotechnology, in conjunction with CSC models, may better elucidate the regulatory mechanisms that govern CSC biology in vivo, as well as develop platforms for targeted theragnostics. It is hoped that the promising applications of the CSC model in HNSCC will eventually alleviate the morbidity and mortality of this pervasive disease.