Insights into the cancer stem cell model of glioma tumorigenesis.
Not all cancer cells are born equal. While the great majority of the cells that make up tumours are destined to differentiate, albeit aberrantly, and eventually stop dividing, a handful of cancer cells appear to possess limitless replicative potential. This review presents compelling evidence to suggest that the bulk of malignant cells of most cancers are generated by a rare fraction of stem cell-like cancer cells. These cells, dubbed cancer stem cells, are phenotypically similar to the normal stem cells of the corresponding tissue of origin, but they exhibit dysfunctional patterns of self-renewal and differentiation. Cancer stem cells that are capable of recapitulating brain tumours as xenografts in mice are characterised by defined stem cell markers. These brain tumour stem cells demonstrate enhanced chemoresistance and radioresistance mechanisms compared to non-stem cells in the heterogeneous tumour, which suggest that they may be the likely candidates for tumour progression and recurrence. Indeed, recent work has shown that such aberrant signalling pathways may be targeted in novel anti-cancer therapeutic strategies. The stem cell concept of tumour progression prompts immediate attention to a new paradigm in cancer research with a focus on this minority subset of cells, and the design of novel therapeutic strategies to target these cells that are insignificant within the population of tumour cells, but that are in fact the relevant cells to be destroyed.
Tang
Carol
C
Department of Research, National Neuroscience Institute, 11 Jalan Tan Tock Seng, Singapore 308433.
Chua
Constance L M
CL
Ang
Beng-Ti
BT
D002471:Cell Transformation, Neoplastic; D005910:Glioma / Q000473:pathology* / Q000532:radiotherapy; D006801:Humans; D008954:Models, Biological; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000473:pathology*; D012846:Singapore