Cancer stem cells: a new framework for the design of tumor therapies

Modern tumor therapy has achieved considerable progress, but many tumors remain refractory to treatment or relapse following initial remission. Recent evidence points to one possible reason for this limited therapeutic efficiency: that the design of anticancer agents so far may not have been aimed at the right target. While conventional tumor therapies have targeted the main mass of tumor cells, there is now compelling evidence that tumor initiation and progression are driven by a subpopulation of tumor cells that possess stem cell properties and are resistant to traditional cancer treatments-the cancer stem cells (CSCs). CSCs have been identified in most types of cancer and can be separated from the rest of the tumor cells using appropriate markers. CSCs are regulated by molecular mechanisms and specific, perivascular, and hypoxic microenvironments, which largely overlap with those controlling stem cells from normal tissues. Our improved understanding of CSC biology has already provided a number of novel targets and drug discovery platforms for the design of specific therapies that aim to eradicate the CSC subpopulation. Therapeutic approaches can be targeted either at eliminating the CSCs themselves or at disrupting the niches in which CSCs reside. Moreover, the importance of CSCs for tumor growth, resistance, and progression implies that clinical trials and preclinical studies of anticancer therapies should include as a key element an assessment of the abundance and persistence of CSCs. Thus, CSC research holds great promise for providing important new impetus to the fields of tumor biology and clinical oncology.