MYCN amplification

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.

P1/2, N=374, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: May 2026 --> May 2027 | Trial primary completion date: May 2026 --> May 2027

We discuss emerging strategies to disrupt MYCN interactions and to enable its degradation through disruption of protein stabilisation mechanisms or the use of degraders such as PROTACs.  By integrating knowledge of MYCN biology, molecular structures and chemical biology, these approaches provide promising routes towards targeted therapies for MYCN-driven neuroblastoma.

P2, N=42, Completed, National Cancer Institute (NCI) | Active, not recruiting --> Completed | Trial completion date: Sep 2026 --> Mar 2026

Combined CHK1/CHK2 inhibitor therapy shows a synergistic anti-tumor effect against neuroblastoma cells. Combination therapy impairs DNA damage response pathways and drives accelerated cell cycle progression in neuroblastoma cells. Combination therapy increases DNA damage, replication stress, and apoptosis marker expression. Combined CHK1/CHK2 inhibition holds therapeutic potential for the treatment of neuroblastoma.

Therefore, we propose that immune IL4i1 is permissive for NB growth and survival. IL4i1 produces context-dependent oncometabolites and, as a secreted enzyme, represents a target for cell death manipulation in cancers sensitive to oxidative stress-driven cell death.

Our review did not uncover features to improve grading of oligodendroglioma, IDH-mutant and 1p/19q-codeleted, although CNS WHO grade 3 tumors with elevated mitotic rates, yet lacking necrosis, microvascular proliferation, CDKN2A/B homozygous deletion and MRI contrast enhancement, may be associated with extended survival. Implementing evidence-based criteria for risk stratification and grading will improve guidance for clinical decision-making.

CDCA7 may serve as a prognostic marker for neuroblastoma. Its silencing leads to G1 cell cycle arrest and a reduction in CDK6 expression, ultimately inhibiting NB cell proliferation.