Abstract
Cancer treatment continues to be challenged by the development of therapeutic resistances and relapses in the clinical setting, which are largely attributed to tumor heterogeneity, particularly the existence of cancer stem cells (CSCs). Thus, targeting the CSC subpopulation may represent an effective therapeutic strategy. However, despite advances in identifying and characterizing CD133(+) CSCs in various human cancers, efforts to translate these experimental findings to clinical modalities have been slow in the making, especially in light of the growing awareness of CSC plasticity and the foreseeable pitfall of therapeutically targeting CSC base sorely on a surface marker. We, and others, have demonstrated that the CD133(+) CSCs reside in complex vascular niches, where reciprocal signaling between the CD133(+) CSCs and their microenvironment may govern niche morphogenesis and homeostasis. Herein, we discuss the multifaceted functional role of the CD133(+) cells in the context of their niche, and the potential of targeting CD133 as a niche-dependent approach in effective therapy.