Stem-like cells and therapy resistance in squamous cell carcinomas.

Cancer stem cells (CSCs) within squamous cell carcinomas (SCCs) are hypothesized to contribute to chemotherapy and radiation resistance and represent potentially useful pharmacologic targets. Hallmarks of the stem cell phenotype that may contribute to therapy resistance of CSCs include quiescence, evasion of apoptosis, resistance to DNA damage, and expression of drug transporter pumps. A variety of CSC populations within SCCs of the head and neck and esophagus have been defined tentatively, based on diverse surface markers and functional assays. Stem-like self-renewal and differentiation capacities of these SCC subpopulations are supported by sphere formation and clonogenicity assays in vitro as well as limiting dilution studies in xenograft models. Early evidence supports a role for SCC CSCs in intrinsic therapy resistance, while detailed mechanisms by which these subpopulations evade treatment remain to be defined. Development of novel SCC therapies will be aided by pursuing such mechanisms as well as refining current definitions for CSCs and clarifying their relevance to hierarchical versus dynamic models of stemness.