Medulloblastoma

P3, N=379, Completed, Children's Oncology Group | Active, not recruiting --> Completed | Trial completion date: Jun 2028 --> Mar 2026

Using a Sonic Hedgehog (SHH)-driven mouse model, two patient-derived xenografts (SHH and group 3), and drug-resistant TP53-mutant MB cells, we found that T3 and cytotoxic chemotherapy suppress tumor growth through complementary biological mechanisms: T3 promotes terminal differentiation of tumor cells, whereas cyclophosphamide (CTX) and irinotecan (CPT-11) induce caspase-3-dependent apoptosis. T3-induced transient tachycardia was effectively controlled with propranolol without compromising antitumor activity. Together, these findings support the potential of T3 as a clinically accessible differentiation-based therapy that enhances chemotherapy responses and suppresses post-treatment tumor regrowth in medulloblastoma.

Outcomes for recurrent medulloblastoma remain unfavorable. However, LCT was associated with improved PFS, while chemotherapy was associated with both improved PFS and OS.

Single cell RNA sequencing revealed that Nestin-expressing GCP have a transcriptome indicating reduced neuronal differentiation and enrichment for stem cell genes compared to bulk GCPs and more closely align with SHH MB cells. Together, our findings reveal functionally important heterogeneity within the GCP lineage and suggest that SHH MB arises preferentially from a small subpopulation of GCPs that express Nestin.

Mechanistic insights were further elucidated through in-depth proteome analyses. Our study qualifies the use of proteomic signatures and activation of neuronal differentiation trajectories to tailor selective therapeutic opportunities for distinct subgroups of patients with medulloblastoma.

ResiPOx enhanced CAR T-cell efficacy by activating myeloid cells and reducing suppressive populations. Conclusions : Optimized CAR design combined with TLR7/8-mediated myeloid reprogramming enhances T cell activity, supporting TME-guided immunotherapy for G3MB.

P1/2, N=68, Not yet recruiting, Washington University School of Medicine | Trial completion date: Apr 2043 --> Jun 2051

Germline P/LP mutations were identified in 15.7% of Korean children and AYAs with CNS tumors, most commonly in gliomas and other CNS tumors. Our findings highlight the molecular heterogeneity of germline predisposition in CNS tumors and emphasize the importance of germline testing for risk assessment and surveillance.

In vitro findings reveal that nanoparticles-mediated miR-326 delivery significantly reduces stemness markers (Nanog and Sox2) and promotes neuronal differentiation, as evidenced by increased β3-tubulin expression. These results highlight polycaprolactone-based nanoparticles as a promising platform for miR-326 delivery, establishing a foundation for future investigations on therapeutic strategies in medulloblastoma.

P1, N=35, Active, not recruiting, Children's Oncology Group | Trial completion date: Feb 2030 --> Dec 2027 | Trial primary completion date: Apr 2027 --> Dec 2027

This study highlights the prevalence, oncogenic content, and conservation of ecDNA in PDX models relative to pediatric patient tumors. We observed that ecDNA frequently recapitulates oncogene amplifications found in human cancers, is generally preserved during PDX establishment, and reflects subtype-specific patterns across tumor types. These findings support the utility of PDX models in studying ecDNA biology in pediatric cancer progression and therapy. Longitudinal sampling during PDX tumor growth and under therapeutic pressure could provide insights into molecular evolution, clonal selection, and ecDNA-driven therapy resistance.

P2, N=3, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: May 2026 --> May 2027