Our recent studies found that a proportion of tumor cells in human and mouse MB, undergo spontaneous terminal differentiation. After the terminal differentiation, tumor cells have lost their proliferative capacity and tumorigenic potential. These studies suggest that MB can be treated by inducing tumor cell differentiation. The differentiation of tumor cells is driven by NeuroD1, a helix-loop-helix transcription factor regulating normal neuronal differentiation. However, NeuroD1 expression is epigenetically repressed by the tri-methylation of lysine 27 (H3K27me3) on histone H3 protein. Inhibition of H3K27me3 by using EZH2 antagonists, promotes tumor cell differentiation through upregulation of NeuroD1. Our studies demonstrate that MB can be treated by inducing tumor cell differentiation. Such differentiation therapy is a promising approach for tumor treatment in that it is more targeted and less toxic, compared with conventional cytotoxic drugs or radiation that non-selectively kill dividing cells.

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