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

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.

Automated summary

While most SHH-MBs respond well to therapeutic intervention, radiation therapy can cause long-term neurocognitive defects, particularly in infants and young children. Attempts to reduce therapy or de-escalate treatment have shown poor outcomes in infant SHH-MBs, potentially due to the existence of therapy-resistant cancer-stem-cell populations driving tumor recurrence.