MYCN amplification

For patients ≥547 days old, any age cut-off ≤40 months discriminated younger (superior EFS/OS) versus older patients; no cut-off was optimal. OCAYA diagnosed 2010-2022 (post-immunotherapy era) had superior outcomes versus 2003-2009. Stratification by comprehensive molecular biomarkers will likely best inform novel therapeutic strategies for OCAYA.

Tumor growth decreased in animals treated with ATUX-1215, and analysis of tumor specimens confirmed decreased MYCN expression. We conclude that pharmacologic PP2A reactivation may be a relevant therapeutic component in NBL treatment through its targeting of MYCN.

ATR inhibitors are a prototype for the development of medicinal products in a limited pediatric population. For the substantial potential of ATR inhibitors in children with malignancy to be realized, strategic planning between academia, industry, regulators, and patient advocates is vital.

CTTA has a potential role in allowing differentiation between neuroblastoma and Wilms tumor. It may additionally allow differentiation among various histological subtypes of neuroblastoma and detection of MYCN amplified neuroblastoma.

In the Th-MYCN/ALKF1174L neuroblastoma mouse model, combination therapy induced complete tumor regression and significantly improved survival rates compared with monotherapies. These findings demonstrate that combining indisulam and alectinib is a promising approach to treating aggressive malignancies such as high-risk neuroblastoma, exploiting the untapped polypharmacology of alectinib as an RNA splicing inhibitor and supporting the therapeutic value of co-targeting interdependent splicing factors for synergistic benefit.

In our experience, MYCN amplification and concomitant extra-CNS metastases at CNS relapse significantly decrease OS. Multimodal treatment, including 131I-omburtamab radioimmunotherapy, significantly improves survival outcomes.

Despite the exploratory nature of the analysis on a small population, the study underscores the biological and transcriptional heterogeneity of LGGs and highlights the limitations of tumor-only sequencing approaches. Broader genomic profiling and matched normal controls are warranted to refine the interpretation of rare or non-canonical variants.

TF activity profiling provides robust stratification for NB, integrating clinical prognostication and immune characterization. This study offers novel insights into TF-driven NB biology, with implications for targeted therapy and immunotherapeutic strategies.

P1/2, N=186, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Dec 2026

Inhibition of SLC25A1 preferentially induced potent apoptosis in MYCN-amplified neuroblastoma cells, and synergistically potentiated the therapeutic efficacies of BCL2 antagonists. These findings reveal SLC25A1 as an actionable MYCN-driven metabolic liability, and validate SLC25A1 inhibitors, alone or in combination with BCL2 antagonists, as potential effective therapeutics for MYCN-amplified neuroblastomas.

Incorporation of a spike-in panel into the Avenio ctDNA assay enabled reliable detection of high-level MYC/MYCN amplifications and fulfilled practical requirements for local reimbursement. The estimated CNV limit of detection in this setting is ≈3 copies. Further replicate testing and validation with clinical specimens are warranted to refine sensitivity and interlaboratory robustness.

The study highlights the importance of collaboration between PBCRs and clinical registries to ensure comprehensive data collection and enhance more informative population-based studies. Future efforts will focus on expanding the linkage to other national clinical registries.