Origins and clinical implications of the brain tumor stem cell hypothesis

With the advent of the cancer stem cell hypothesis, the field of cancer research has experienced a revolution in how we think of and approach cancer. The discovery of "brain tumor stem cells" has offered an explanation for several long-standing conundrums on why brain tumors behave the way they do to treatment. Despite the great amount of research that has been done in order to understand the molecular aspects of malignant gliomas, the prognosis of brain tumors remains dismal. The slow progress in extending the survival of patients with malignant CNS neoplasms is very likely due to poor understanding of the cell of origin in these tumors. This review article discusses the progress in our understanding of brain tumor stem cells as the cell of origin in brain cancers. We review the different proposed mechanisms of how brain tumor stem cells may originate, the intracellular pathways disrupted in the pathogenesis of BTSCs, the molecular markers used to identify BTSCs, the molecular mechanisms of cancer initiation and progression, and finally the clinical implications of this research.