First among equals: the cancer cell hierarchy

Primary cancer cells exhibit heterogeneity in their proliferative ability. The cancer stem cell (CSC) model accounts for this heterogeneity by proposing that each cancer consists of a small population of CSCs that are capable of unlimited growth and self-renewal and a much larger population of cells, descendants of the CSCs, that have lost self-renewal capacity. The CSC model has important implications for cancer therapy. Eradication of CSCs, the cells responsible for maintenance of the neoplasm, would be necessary and sufficient to achieve cure. By extension, both the frequency of stem cells in a tumor and their propensity to undergo self-renewal (Psr) would have a direct impact on the curability of that tumor. The Psr is a critical biological characteristic of CSCs-small differences in Psr have enormous impact on the probability of success in cancer therapy. Differentiation therapy, defined as treatment that reduces the Psr of CSCs, is one approach to targeting CSCs.