The Difficulty of Targeting Cancer Stem Cell Niches

Normal stem cell niches typically are identified by their distinctive anatomical features and by association with tissue-specific stem cells. Identifying cancer stem cell (CSC) niches presents a special problem because there are few if any common anatomical features among tumors, and the physical phenotypes that reportedly describe the CSCs as entities may be subject to the host's microenvironment, sex, and tumor stage. Irrespective of a niche's location, the occupant's phenotype, or the precise molecular composition, all niches must do basically the same thing: maintain the activities in a stem cell that define it as such. Therefore, a potentially successful strategy, both for elaborating a molecular and cellular portrait of a CSC niche, and for therapeutically targeting them, is to identify components in the tumor microenvironment that are required for maintaining the functions of self-renewal, differentiation, and quiescence in the face of cytotoxic therapeutic regimens.