MYCN amplification

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.

Oncogene amplification and/or p53 pathway abnormalities and/or typical SCAs identify patients with intermediate-risk neuroblastoma with inferior outcome for whom intensified or alternative treatments should be considered.

P2, N=286, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Jun 2026 --> Jun 2027 | Trial primary completion date: Jun 2026 --> Jun 2027

This work demonstrates the therapeutic potential of the RALA/mGPC2 vaccine for treating neuroblastoma. Additionally, GPC2 is upregulated across multiple adult and pediatric cancer subtypes, establishing this vaccine as an attractive immunotherapy with far-reaching potential.

Coarse calcification observed in CT imaging serves as a crucial prognostic indicator in pediatric neuroblastoma, closely linked to tumor aggressiveness, early distant metastasis, and decreased survival rates. This study advocates for the integration of calcification classification into neuroblastoma prognostic assessment systems and establishes a basis for future investigations into the molecular mechanisms related to calcification and potential targeted interventions.

Our results suggest that MYC-dependency likely depends on many factors including, but not limited to, total copy number of the detected amplification, lineage specific factors, concomitant presence or absence of additional oncogenic alterations, and in some cases amplification focality.

Multiplexed imaging showed broad but heterogeneous HER2 expression across tumor states in both cases; in the MYCN-amplified tumor, this occurred alongside EGFR/MAPK-enriched proliferative niches, whereas the ZFTA-RELA tumor showed more diffuse organization without strong coupling of EGFR and proliferation. These findings provide early clinical evidence supporting HER2-directed ADCs in ependymoma and highlight the value of integrated molecular and spatial profiling in interpreting therapeutic response in rare CNS tumors.

This study systematically elucidated the crucial role of lipid metabolic reprogramming in the pathogenesis of HR MYCN-NA NB. These findings provide critical insight for uncovering the mechanisms underlying NB progression and for identifying potential therapeutic targets.

Structure-based virtual screening identified several candidate inhibitors of NDUFS6, including guanosine 5'-triphosphate (disodium salt), 1,4-β-D-xylopentaose, and deferoxamine...NDUFS6 is significantly upregulated in HR-NB and contributes to tumor aggressiveness by promoting proliferation, migration, and invasion, accompanied by activation of metabolic pathways and suppression of neuronal differentiation and immune responses. Virtual screening identified guanosine 5'-triphosphate (disodium salt) as a potential NDUFS6 inhibitor with efficacy in both MYCN-amplified and non-amplified cells, highlighting NDUFS6 as a promising therapeutic target and providing a rationale for targeted intervention in HR-NB.

Despite high cytotoxicity, however, NF-YAx selects a resistant subpopulation with mesenchymal/neural crest stem cell-like identity, unveiling a doxorubicin-induced NF-YAx-dependent resistance mechanism, with potential to influence post-therapeutic relapse and disease progression. Therefore, evaluating alternative NF-YA splicing, and especially NF-YAx expression, in advanced stage and post-therapeutic relapsed NBs, may be of both prognostic and therapeutic significance.

Understanding the underlying mechanisms involved in RB and exploring new treatment strategies is a crucial step toward developing more effective and less invasive therapeutic approaches that can improve patient outcomes. This review summarizes the significant genetic and epigenetic alterations involved in RB tumorigenesis, current therapeutic strategies, and future treatment prospects for patients with RB.

Maximal safe resection remains the cornerstone of management, with radiotherapy or chemotherapy reserved for selected cases. Despite potential morbidity, long-term survival and functional outcomes are favorable for many patients.