Medulloblastoma

Prospects encompass the enhancement of drug delivery methods, the integration of SHH inhibitors with alternative therapeutics, and the advancement of next-generation inhibitors to surmount resistance. Hence, these developments offer potential for improving outcomes in SHH-MB while reducing side effects, especially in pediatric populations.

Intratumoral mitoxantrone administration in a murine CD24-high glioma model extended survival, decreased tumor size, reduced Siglec-10+/TREM2+ cell populations, and increased anti-tumor CD8+ cells. These findings suggest that targeting the CD24/Siglec-10 axis with mitoxantrone may modulate the tumor microenvironment and enhance anti-tumor immunity. Keywords: CD24, Siglec-10, Mitoxantrone, Malignant brain tumor, Immunotherapy.

The combination of WEE1 inhibitor adavosertib and vinca alkaloid vincristine demonstrated the highest activity, which was validated in TP53mut SHH-MB patient-derived organoids. Despite the drugs' limited efficacy in the in vivo PDX model, WEE1 knockdown led to significant growth reduction in in vitro and in vivo TP53mut SHH-MB models. Our findings identify WEE1 as a promising target in LFS SHH-MB, suggesting its inhibition combined with vincristine treatment as a potential chemotherapeutic strategy.

In particular, here we report on the identification of CK2-TN03, a CK2 inhibitor showing greater selectivity and cellular efficacy than silmitasertib, the only available clinical grade CK2 inhibitor with orphan status for cholangiocarcinoma and in clinical trials for medulloblastoma...Accordingly, neuroblastoma cells persistently stall in mitosis before going to apoptosis. Finally, CK2-TN03 does not affect noncycling cells and significantly reduces tumor growth in mice xenografts without any apparent toxicity.

P1, N=71, Active, not recruiting, National Cancer Institute (NCI) | N=110 --> 71 | Trial completion date: Dec 2025 --> Jan 2027

P=N/A, N=184, Recruiting, St. Jude Children's Research Hospital | Initiation date: Dec 2025 --> Mar 2026

Unexpectedly, we demonstrated that MYC triggers lipid storage, creating a unique dependency on lipid droplet-mitochondria communications to sustain tumor maintenance in vivo. Together, this comprehensive analysis reveals a targetable vulnerability downstream of MYC that constitutes a promising therapeutic approach to treat currently untreatable medulloblastoma subtypes.

P2, N=1376, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: May 2026 --> Jan 2027

These findings provide new structure-function insights into a key signaling complex mutated in cancer and other diseases. Summary: Alphafold3 predicts a more extended interaction of the GLI1 transcription factor with the tumor suppressor SUFU than has been seen in published x-ray structures; these predictions are supported by structure-function experiments, including analysis of patient-derived missense variants of SUFU.

Cyclin D1 can be used as a complementary marker in WNT-AG detection. ROR2 negativity may indicate G3 tumors, though further studies are warranted to confirm its prognostic value.

Meta-analyses of clinical data reveal that neonatal hyperbilirubinemia (jaundice) caused by high levels of bilirubin, increases pediatric brain tumor risk. Collectively, these findings highlight the origins of sex differences in neurodevelopment and brain tumorigenesis, offering insights into early screening and prevention of pediatric brain tumors through targeted interventions addressing modifiable risk factors.

In flies, reduction of PARP activity ameliorated the tumor associated phenotypes of SA1-deficient tissue. Our in vivo and in vitro data suggest that impairment of PARP activity compensates for reduced cohesin activity, highlighting a vulnerability that might be pharmacologically exploited in brain tumors.