MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)

Conversely, in prostate adenocarcinoma models, DNMT1 deletion leads to de-repression of neuroendocrine lineage genes with a loss of H3K27me3 marks. Our findings reveal a functional interplay between two repressive epigenetic machineries that mediates lineage plasticity in prostate cancer.

The presence of diffuse systemic metastasis, axial bone involvement, or skull metastasis is strongly associated with poorer prognosis in pediatric patients with high-risk stage 4 neuroblastoma. Furthermore, axial bone metastasis, diffuse bone metastasis, Curie score>2, MYCN amplification, and 11q23 deletion constitute independent predictors of unfavorable clinical outcomes.

Treatment with DT-061 combined with its inactive competitive antagonist, DT-766, and the proteasome inhibitor, MG-132, reversed this effect on the loss of N-Myc protein expression, suggesting that PP2A-B56α modulation affects N-Myc stability via the proteasomal degradation pathway. In a xenograft model, we observed tumor growth inhibition upon DT-061 treatment, along with a reduction in N-Myc protein expression in vivo. Combined, these results highlight the importance of the PP2A tumor suppressor in regulating MYCN oncogenic signaling and open new potential treatment regimens for high-risk neuroblastoma patients.

This score reliably predicted recurrence risk and identified EMT-prone microenvironments, with stronger predictive performance in nontumor tissues, suggesting its potential in detecting precancerous niches predisposed to de novo tumorigenesis. Collectively, our findings establish MYCN as a functional driver and spatial marker of tumor-promoting microenvironments in liver tumorigenesis; additionally, we propose a clinically actionable strategy to identify high-risk patients through transcriptomic profiling of nontumor liver tissue.

P3, N=225, Recruiting, Children's Oncology Group | Trial completion date: Dec 2027 --> Dec 2029 | Trial primary completion date: Dec 2027 --> Dec 2029

P2, N=45, Active, not recruiting, Children's Oncology Group | Trial completion date: Jun 2027 --> Mar 2028 | Trial primary completion date: Jun 2027 --> Mar 2028

Continued progress will depend on integrating molecular profiling into clinical decision-making, refining risk-adapted treatment strategies, and expanding international collaborative research efforts. This narrative review summarizes current knowledge on neuroblastoma epidemiology, biology, staging, and treatment, highlighting recent advances and future directions aimed at improving outcomes for affected children.

Patients with relapsed HR-NBL have poor outcomes with median OS < 2 years. Time to relapse was a significant predictor of OS.

In addition, partial regression of FGFR1N546K mutant tumor lesions occurred upon treatment with the FGFR inhibitor futibatinib and low-intensity chemotherapy in a patient with refractory neuroblastoma. Together, our data demonstrate that FGFR1N546K is a strong oncogenic driver in neuroblastoma that is associated with failure of current standard chemotherapy, and suggest potential clinical benefit of FGFR-directed therapies in FGFR1 mutant high-risk patients.

P1, N=26, Completed, Dana-Farber Cancer Institute | Active, not recruiting --> Completed

This study uncovered a novel oncogenic axis in neuroblastoma, where NeuroD1 transcriptionally upregulates USP1, promoting N-Myc stabilization and tumor progression. Furthermore, the findings highlight the therapeutic potential of repurposing Pimozide as a promising treatment strategy for this aggressive tumor subtype.