Medulloblastoma

ICIs show manageable safety but limited efficacy in unselected pediatric CNS tumors. Durable benefit is most evident in RRD/hypermutant biology and possibly PD-L1-high niches (e.g., some low-grade gliomas and CNS-GCT). Future trials should be biomarker-driven and pair ICIs with priming combinations (e.g., radiation, epigenetic modulators, metronomic chemotherapy) to convert "cold" tumors into responders.

We review the characteristics of MET-altered pediatric high-grade glioma using the Open Pediatric Brain Tumor Atlas (Open PBTA) and published series, which suggests that MET fusions may be enriched in RIGs. Our two cases highlight the promising CNS penetration and on-target activity of capmatinib in MET-altered glioma; however, the development of rapid resistance emphasizes the pressing need to develop combination and/or new therapies for RIG.

P=N/A, N=38, Not yet recruiting, Ruijin Hospital

P1, N=51, Recruiting, Sun Yat-sen University

Furthermore, known Ded1 target genes with relatively unstructured 5' UTRs showed upregulated protein levels in rapamycin. We thus hypothesize that mutant DDX3X selectively upregulates translation of unstructured, pro-growth transcripts while downregulating other structured transcripts, allowing tumor cells to bypass stress-induced growth controls and promoting medulloblastoma progression.

P=N/A, N=800, Active, not recruiting, British Columbia Cancer Agency | Trial primary completion date: Sep 2025 --> Sep 2026

Consistent with this targeted delivery, we observed a substantial decline in intratumoral Gli1 and Ptch1 expression, confirming effective SHH pathway modulation. Together, these findings propose a promising nanotechnology-based method to improve phenformin therapeutic index in SHH MB by enhancing tumor specificity and reducing systemic toxicity.

P1, N=20, Active, not recruiting, Valent Technologies, LLC | Recruiting --> Active, not recruiting

In pediatric patients with metastatic medulloblastoma, primary tumor resection might be avoidable. A biopsy-based approach followed by timely multimodal therapy can preserve survival outcomes while minimizing surgical risks, as long-term prognosis is likely related to the disease subtype and prompt oncological treatment. The proposed strategy warrants further investigation and might have broader implications for medulloblastoma treatment paradigms.

These findings indicate a subgroup-specific role for TNIK in MB biology and suggest its potential utility as a prognostic biomarker, particularly in Group 4 MBs.

Moreover, these components are characterized by distinct molecular alterations from primary CNS tumors, without C19MC alterations for ETMRs, with an overrepresented SHH-subgroup for medulloblastomas, and with an epigenetic profile distinct from CNS counterparts in ovarian ependymomas. These data need to be confirmed before they can be incorporated into future patient personalized treatment.

While germline NF2 mutations (NF2-SWN) often lead to meningiomas and vestibular schwannomas, somatic NF2 mutations are common in sporadic meningiomas and should not suggest NF2-SWN. This case highlights the need to correlate small enhancing IAC foci with morphology on CISS MRI, symmetry, longitudinal stability, and NF2 pathology to avoid misdiagnosis of enhancing Scarpa's ganglia as vestibular schwannomas, as misdiagnosis can lead to increased patient anxiety and unnecessary follow-ups.