Cancer stem cells in glioma: challenges and opportunities

Abstract

The discovery of cancer stem cells in glioma has created a paradigm shift in our understanding of this deadly disease. Glioma stem cells exhibit sustained self-renewal and potent tumorigenic potential and differ from their more differentiated progeny in response to current therapies. Recurrent disease is likely derived from glioma stem cells or progeny reprogrammed to gain stem cell-like phenotypes, indicating that the stem cell phenotype is a crucial therapeutic target. While debate over cancer stem cell and clonal evolution models persists, important knowledge has been gained over the past decade from glioma stem cells investigation and clinical impact is expected.

Keywords: Glioma; cancer stem cells.

Figure 1

Modeling cellular heterogeneity of cancer. (A) The stochastic model assumes that cancer cell phenotypes are primarily defined by intrinsic factors, in particular driver mutations. It indicates a clonal evolution of cancer. However, this model may not adequately address phenotypic variations within individual clones; (B) The cancer stem cell model assumes that cancer is organized in a hierarchical structure that, at least in part, resembles that of the tissue of origin. Tumorigenic potential is limited to the cancer stem cell subpopulation. In addition, cellular heterogeneity of the cancer is a product of multipotent cancer stem cells. However, the maintenance of coexisting genetically distinct clones in most late-stage cancers has not been adequately addressed by this model; (C) Emerging evidence suggests a combination of these two models in which cancers are driven by one or multiple dominating clones, some of which may be organized in a hierarchical manner. However, at the time of diagnosis, the original hierarchy may be altered due to acquisition of genetic or epigenetic events that promote tumorigenic capacity and impair differentiation.