Medulloblastoma

Upfront CTx only regimens used were classified into three groups to reflect disease treatment conventions: standard-dose, high-dose (intensified regimens of sufficient dosage to require stem cell support) and those including intraventricular methotrexate (IVT-MTX)...With outcomes established, clinical trials are now encouraged to focus on quality-of-life following different intensified approaches to identify the kindest curative strategies. Cancer Research UK, Children with Cancer UK, Children's Cancer North, Star for Harris, JGW Patterson Foundation, Little Hero and Blue Skye Thinking.

Notably, cross-omics functional concordance increased with radiation dose, revealing greater integration of molecular responses following high-dose irradiation. Together, these findings define dose-specific molecular states associated with radiation-induced MB and provide a biological framework linking early cerebellar remodeling to tumor heterogeneity, with implications for pediatric radiation risk assessment and therapeutic stratification.

As a result, conditional knockout of Zdhhc13 in cerebellar granule neuron precursors (GNPs) significantly alleviates the severity of MBSHH induced by constitutively active Smoothened (Smo-M2) overexpression and markedly extends overall survival, whereas knockout of Abhd17a increases the incidence of MBSHH induced by Patched-1 ablation, rather than its progression. Together, these findings uncover the dynamic regulation of GLI1 palmitoylation and depalmitoylation by the ZDHHC13 and ABHD17A and subsequent GLI1 stabilization and destabilization as a hitherto uncharacterized mechanism controlling SHH/GLI1 signaling and may provide additional targets for therapeutic intervention of MBSHH.

As a result, low expression of RNF138 in human MBSHH correlated with high GLI1 protein level, whereas overexpression of RNF138 downregulated GLI1 to suppress the growth of human MBSHH Daoy cells xenografts. Taken together, these results uncover GLI1 polyubiquitination by RNF138 as a hitherto uncharacterized mechanism governing SHH signaling and may serve as an additional therapeutic target in SHH-driven malignancies.

These preclinical findings suggest that combining immune priming with sublethal LDXR, Gal-3 inhibition, and 4-1BB activation may be an effective treatment strategy for G3MB.

P1, N=30, Not yet recruiting, Children's National Research Institute

Aberrantly low levels of AMBRA1 occurring in Sonic Hedgehog-type medulloblastomas correlate with high levels of p21Waf1/Cip1 and a worse prognosis. Finally, AMBRA1 and p21 levels may serve as biomarkers for patient stratification and treatment in medulloblastoma.

Conflicting reports show that it is a biomarker for response to cisplatin and a prognostic factor in some brain tumors, such as medulloblastomas, but can even be a negative prognostic factor in others, like glioblastomas...In brain tumors such as medulloblastomas and primary central nervous system lymphomas (PCNSL), when total cell killing can be expected by chemotherapy and/or chemoradiotherapy, high SLFN11 expression is a positive prognostic marker. However, SLFN11 can also be highly expressed in mesenchymal tumors, and in cases where total cell killing cannot be achieved, widespread relapse can accompany an initial response.

P1, N=41, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Apr 2026 --> Sep 2026

P=N/A, N=450, Recruiting, West China Hospital

We validated PCK2 as a driver of proliferation, migration, invasion, glycolysis, and M2 macrophage polarization in MYC-amplified MB cells through short hairpin RNA knockdown experiments. Together, our findings establish metabolic-TIME crosstalk as a prognostic determinant and proffer PCK2 as a therapeutic target for aggressive MB subtypes, offering insights into metabolic subtyping and precision therapy strategies to improve clinical outcomes.

P1, N=30, Active, not recruiting, Daniel Landi | Trial completion date: Apr 2026 --> May 2027