Cancer stem cells and survival pathways.
Gliomas and medulloblastomas are the most frequent malignant brain tumors in adult and children respectively. Although both tumors arise in the CNS, there is a significant difference in their therapeutic response. Medulloblastomas are relatively curable, while glioblastomas are basically incurable. During the last decade several reports have demonstrated the existence of cancer stem cells in brain tumors, their location and their response to treatment. We have recently described the therapeutic response of medulloblastomas to radiation in their native microenvironment, illustrating how p53 and Pi3K signaling pathways lead to the evasion of cell death by the nestin-expressing cells in the perivascular stem cell niche, even while the bulk of tumor succumbs to apoptosis.(1) It remains to be determined whether this mechanism of tumor resistance applies to the more complex stem-cell niche and tumor bulk of gliomas.
Hambardzumyan
Dolores
D
Department of Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
Becher
Oren J
OJ
Holland
Eric C
EC
D000818:Animals; D001932:Brain Neoplasms / Q000532:radiotherapy*; D006801:Humans; D007381:Intermediate Filament Proteins / Q000378:metabolism; D008527:Medulloblastoma / Q000532:radiotherapy*; D051379:Mice; D008954:Models, Biological; D014411:Neoplastic Stem Cells / Q000528:radiation effects*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051880:Receptors, Notch / Q000378:metabolism; D015398:Signal Transduction / Q000528:radiation effects*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D007381:Intermediate Filament Proteins; C577484:NES protein, human; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D051880:Receptors, Notch; D016159:Tumor Suppressor Protein p53; D019869:Phosphatidylinositol 3-Kinases