Targeting stem cells in brain tumors.

Abstract

Stem cells are commonly defined as undifferentiated cells capable of self-renewing and giving rise to a large number of differentiated progeny. It is becoming increasingly apparent that there exist cancer stem cells (CSCs) from which the cells of any given malignancy arise, whereby only a few cells out of a population of cancer cells are able to initiate tumor formation. These CSCs, like their normal counterparts, are characterized by self-renewal and the ability to "differentiate" into all of the cell types in the original tumor. Current chemotherapeutic strategies involve using non-specific cytotoxic agents that target rapidly cycling cells. Although this may reduce disease burden in many cases, these therapies may miss the rare, self-renewing population that truly gives rise to the malignancy (the CSC). This review will focus on the recent discovery of stem cell-like cells in human brain tumors, putative "brain cancer stem cells," which exhibit the properties of self-renewal and the ability to recapitulate the original tumor heterogeneity. Dissecting the molecular mechanisms that underlie the ability of these cells to self-renew and maintain quiescence may allow the development of novel therapeutic strategies that will allow for more efficacious and less toxic therapies for these devastating malignancies.