The neurobiology of neurooncology

Abstract

The histological classification of brain tumors currently is based on the morphological appearance and protein expression patterns that reflect specific cell types within the central nervous system. Recent studies have suggested that the cells of origin for brain tumors may persist in the fully formed tumors, and that these "cancer stem cells" might represent the relevant cellular targets for anticancer therapy. In this regard, insights into the developmental neurobiology of brain tumors has significant impact on our understanding of the molecular and cellular pathogenesis of these devastating cancers, as well as the development of new strategies for treating brain tumors.

Genetic Alterations in Mouse Medulloblastomas and Generation of TumorsDe novofrom Primary Cerebellar Granule Neuron Precursors

“…This entire process is terminated by P21. It is thought that a subset of medulloblastomas originates from CGNPs that fail to exit the cycle and migrate, thus yielding tumor cells that mainly arise at the cerebellar periphery (11,12).…”

Developmental signaling pathways in brain tumor‐derived stem‐like cells

“…Due to limited availability of many adult tissue stem cell markers, the geneology of isolated BTSCs is yet to be determined, and the origin of the BTSCs in brain tumors is a subject of debate (Clarke et al, 2006). Evidence exists for both neoplastic transformation of resident NSC as well as reacquisition of stem cell properties by progenitor or differentiated cells (Holland et al, 2000;Dai et al, 2001;Jackson et al, 2006;Kang et al, 2006;Krivtsov et al, 2006;Read et al, 2006;Zhang et al, 2006a;Sharif et al, 2007;Shiras et al, 2007). Aside from direct neoplastic transformation, BTSCs may also arise from disruptions in the stem cell niche or tumor stroma leading to unregulated proliferation and self-renewal (Clarke et al, 2006), such as postulated after disruption of Notch-mediated lateral inhibition.…”

“…Rapid proliferation and high motility are hallmarks of both development and tumorigenesis; therefore, pathways important for development are probable targets for oncogenic transformations (Wechsler-Reya and Scott, 2001;Vogelstein and Kinzler, 2004;Kelleher et al, 2006;Read et al, 2006). The persistence of neural stem cells into adulthood in the subventricular zone and subgranular zone of the hippocampus (Gage et al, 1995;Eriksson et al, 1998;Morshead and van der Kooy, 2001) also provide a pool of candidate cells for oncogenic transformation because of their extended lifespan and cellular machinery for unlimited growth.…”

Chromosomal heterogeneity and instability characterize pediatric medulloblastoma cell lines and affect neoplastic phenotype

“…This tumor arises from cerebellar stem and precursor cells and has a tendency to metastasize via cerebrospinal fluid (Read et al 2006;Louis et al 2007). Current management strategies have achieved a 5-year survival rate of 60-80 % (Packer and Vezina 2008).…”