MYCN amplification

We also found that karyotype has limited utility in the setting of NB. Based on this data, we developed an institutional workflow for NB, including MYCN FISH, CMA, and NGS.

This review aims to analyze the multi-faceted factors influencing the response to immunotherapy in neuroblastoma, including: (1) the inherent immunosuppressive properties of the tumor microenvironment, such as infiltration of myeloid-derived suppressor cells and tumor-associated macrophages, as well as checkpoint molecules and metabolic barriers; (2) tumor cell-intrinsic characteristics, such as low tumor mutational burden, MYCN amplification-associated downregulation of MHC-I, and heterogeneity of GD2 antigen expression; (3) host factors, such as systemic immune status and Fc receptor polymorphisms; and (4) treatment-related factors, such as combination strategies and the development of novel immunotherapeutic products. A deep understanding of these interrelated factors is crucial for developing predictive biomarkers, designing novel combination strategies and next-generation immunotherapies, and ultimately achieving precise immunotherapy for neuroblastoma.

Despite achieving complete remission faster, patients with MYCN-A have a higher probability of recurrence compared with those without MYCN-A.

While arsenic trioxide (As(III)) demonstrates therapeutic potential through ferroptosis induction, its clinical application is severely constrained by dose-limiting systemic toxicity and consequent inflammation-mediated COX2/PGE2 pathway activation, which confers ferroptosis resistance...TCADS comprises two rationally designed self-assembling peptides incorporating As(III)-binding domains, tumor-selective targeting moieties (MMP9-responsive and Tenascin C-targeting motifs), and the COX2 antagonist naproxen (NPX)...This precision-targeted approach empowers TCADS to effectively disrupt the deleterious inflammation-ferroptosis resistance cycle, thereby successfully overcoming treatment resistance and suppressing tumor progression by 85.0% and 95.4% in subcutaneous and orthotopic tumor models, respectively. This integrated paradigm of precision-targeted delivery coupled with microenvironment modulation establishes a compelling therapeutic framework for chemoresistant HR-NB and potentially other MYCN-amplified malignancies.

We also developed a simplified MLPA-based classifier targeting six loci on chromosomes 7, 8, and 11 (SEE-6-CNA), which enabled robust and clinically feasible prognostic stratification. Overall, our findings confirm that the molecular subgroup-specific features of Japanese MBs are largely concordant with global observations and that SEE-6-CNA provides a cost-effective tool to support individualized treatment planning, particularly in resource-limited settings.

Western blotting confirms upregulation of epithelial and downregulation of mesenchymal markers, with inhibited wound closure in SH-SY5Y cells. This nanotherapy disrupts EZH2-E-Cadherin interaction, offering novel translational potential for NB treatment.

In conclusion, BML-284 is a potent USP7 inhibitor that exerts anti-NB activity by regulating the USP7-N-Myc axis. This study not only provides a new candidate for high-risk NB treatment but also offers a framework for the development of USP7 inhibitors.

This review summarizes RB pathogenesis, including RB1 loss, MYCN amplification, epigenetic dysregulation (e.g., METTL3-mediated m6A), and dysregulated pathways (PI3K/AKT/mTOR, Hedgehog), and highlights CRISPR-engineered organoids for identifying cone precursors as tumor origins and validating therapies (CDK4/6 inhibitors and sunitinib)...Future efforts should integrate multiomics, refine vascularization via 3D bioprinting, and develop immunocompetent models to address the disparity between preclinical research and clinical application. Organoid technology has the potential to advance personalized therapies and ultimately enhance the survival and quality of life of patients with RB worldwide.

P1/2, N=174, Active, not recruiting, Monte Rosa Therapeutics, Inc | Recruiting --> Active, not recruiting

It eliminates both non-MYCN-amplified (SH-SY5Y and SK-N-SH) and MYCN-amplified (SMS-KCNR) NB cells that exhibit PMA-inducible CCL2 expression but not MYCN-amplified NB cells (IMR-32 and NB-1) that exhibit CCL2 repression, and is offset by reciprocal NB cell-induced Fas-mediated Jurkat cell apoptosis. These findings form a solid foundation for further pre-clinical development aimed at identifying clinically relevant physiological immune cell equivalents and alternative PKC activators, with the ultimate goal of translating this mechanism into an effective immune-therapeutic approach for the treatment of high-risk non-immunogenic NBs, especially NBs that exhibit CCL2 and TrkAIII expression.

Leveraging this property, neuroblastoma-derived exosomes can be purified, modified, and loaded with small interfering RNA (siRNA) to silence MYCN expression, combined with chloroquine-an FDA-approved autophagy inhibitor-to simultaneously inhibit autophagy and induce apoptotic signaling...Collectively, exosome-based strategies represent a paradigm shift in formulating combination therapies, offering a multifaceted approach to target MYCN amplification, inhibit autophagy, induce apoptosis, and modulate the tumor-microbiome axis. These innovations hold significant promise for improving clinical outcomes in high-risk MYCN-amplified neuroblastoma patients.