Medulloblastoma

P1/2, N=68, Recruiting, Washington University School of Medicine | Not yet recruiting --> Recruiting

This overexpression promotes the self-renewal of MB stem-like cells through the modulation of ERK signaling, thereby contributing to enhanced cancer stemness. Our findings identify NTN1 as a novel downstream effector of the SHH/GLI pathway and demonstrate that quantifying NTN1 levels can refine molecular classification of SHH-subtype medulloblastomas-distinguishing tumors with high SHH pathway activation and enhanced stem-like properties, with potential implications for prognosis and targeted therapy selection.

The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply.The Editor sincerely apologizes to the readership for any inconvenience caused, and we thank the reader for bringing this matter to our attention. [International Journal of Oncology 733‑744, 2011; DOI: 10.3892/ijo.2010.883].

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.