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Stem-Like Cell Populations, p53-Pathway Activation and Mechanisms of Recurrence in Sonic Hedgehog Medulloblastoma

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Abstract

While most Sonic Hedgehog-associated medulloblastomas (SHH-MBs) respond to therapeutic intervention, radiation therapy often causes deleterious long-term neurocognitive defects, especially in infants and young children. To limit neurological comorbidities, the development of a reduction-of-therapy treatment or de-escalation approach was investigated. Although retrospective analysis of MBs indicated low-dose therapy was potentially effective, clinical de-escalation trials showed poor outcomes in infant SHH-MBs and was prematurely terminated. Recent studies suggest the existence of cancer-stem-cell (CSC)-like cell populations that are more resistant to therapies and drive tumor recurrence. This review will discuss the mechanism of these CSC-like cells in SHH-MBs in resisting to p53-pathway activation, which may contribute to the disappointing outcomes of the recent de-escalation trials.

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Acknowledgements

This study was supported by National Institutes of Health (2P01 CA085878-10A1) and National Institute of Neurological Disorders and Stroke (R01 NS053900).

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Authors and Affiliations

  1. Gilbert Family Neurofibromatosis Institute, Children’s National Hospital, Washington, DC, 20010, USA

    Daniel Treisman, Yinghua Li & Yuan Zhu

  2. Center for Cancer and Immunology Research, Children’s National Hospital, Washington, DC, 20010, USA

    Daniel Treisman, Yinghua Li & Yuan Zhu

  3. Center for Neuroscience Research, Children’s National Hospital, Washington, DC, 20010, USA

    Daniel Treisman, Yinghua Li & Yuan Zhu

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  1. Daniel Treisman
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  2. Yinghua Li
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  3. Yuan Zhu
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Correspondence to Yuan Zhu.

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Treisman, D., Li, Y. & Zhu, Y. Stem-Like Cell Populations, p53-Pathway Activation and Mechanisms of Recurrence in Sonic Hedgehog Medulloblastoma. Neuromol Med 24, 13–17 (2022). https://doi.org/10.1007/s12017-021-08673-z

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  • DOI: https://doi.org/10.1007/s12017-021-08673-z

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