In Search of the Medulloblast: Neural Stem Cells and Embryonal Brain Tumors

In many ways, medulloblastomas represent the apotheosis of tumor stem cell concepts. They can arise (at least in animal models) from stem or progenitor cells. They resemble stem cells in terms of their primitive appearance and proclivity for divergent differentiation. Perhaps most importantly, they contain a subset of stem-like cells required for tumor propagation. As discussed previously, however, the relatively faithful adherence of medulloblastoma to the developmental program of nonneoplastic neural stem cells may represent an Achilles heel. Therapeutic regimens targeting Notch and other signaling pathways required in nonneoplastic neural stem cells may also be effective in depleting medulloblastoma stem cells. A better understanding of which germinal epithelia or stem cell populations give rise to medulloblastoma and which molecular pathways drive this neoplastic transformation is critical for such therapeutic advances.