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Deregulated proliferation and differentiation in brain tumors

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Abstract

Neurogenesis, the generation of new neurons, is deregulated in neural stem cell (NSC)- and progenitor-derived murine models of malignant medulloblastoma and glioma, the most common brain tumors of children and adults, respectively. Molecular characterization of human malignant brain tumors, and in particular brain tumor stem cells (BTSCs), has identified neurodevelopmental transcription factors, microRNAs, and epigenetic factors known to inhibit neuronal and glial differentiation. We are starting to understand how these factors are regulated by the major oncogenic drivers in malignant brain tumors. In this review, we will focus on the molecular switches that block normal neuronal differentiation and induce brain tumor formation. Genetic or pharmacological manipulation of these switches in BTSCs has been shown to restore the ability of tumor cells to differentiate. We will discuss potential brain tumor therapies that will promote differentiation in order to reduce treatment resistance, suppress tumor growth, and prevent recurrence in patients.

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Acknowledgments

A.I.P. was supported by the TDC Foundation, the Guggenhime Endowment Fund, the National Brain Tumor Society, and National Institute of Health (U54CA163155 and R21NS088114). F.J.S. was supported by the Swedish Childhood Cancer Foundation, the Swedish Cancer Society, the Swedish Research Council, the Ragnar Söderberg Foundation, the Swedish Society of Medicine, the Åke Wiberg Foundation and the Association for International Cancer Research/Worldwide Cancer Research.

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Swartling, F.J., Čančer, M., Frantz, A. et al. Deregulated proliferation and differentiation in brain tumors. Cell Tissue Res 359, 225–254 (2015). https://doi.org/10.1007/s00441-014-2046-y

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