MYCN amplification

Notably, LY6E emerged as the most prognostically significant gene within the signature. More importantly, we revealed that LY6E modulates M2-type macrophage polarization in neuroblastoma for the first time, suggesting a novel mechanism through which it may contribute to shaping an immunosuppressive tumor microenvironment.

P2, N=10, Not yet recruiting, Shaare Zedek Medical Center

P2, N=153, Completed, St. Jude Children's Research Hospital | Active, not recruiting --> Completed

Clinically, TWIST1+TAC+ CTCs were significantly enriched in the blood samples of metastatic NB patients compared to the non-metastatic group. As a proof-of-principle study, we further demonstrated that the TACR1 antagonist aprepitant could effectively suppress endothelial senescence, tumorigenesis, and CTC-mediated metastatic progression in vivo, presenting a potential therapeutic strategy for NB patients with TAC1-TACR1 activation.

We show that CDK2-Cyclin A2 bind ASCL1 in less responsive cells, with CDK-mediated phosphorylation of ASCL1 limiting the ability of ASCL1 to drive differentiation. Implications: Our study reveals that context-dependent interactions of ASCL1 with protein partners on the chromatin control its ability to re-engage a differentiation program in neuroblastoma.

In SK-BE (2) cells, these ASO prodrugs, particularly the R3‑5 and R5‑5 sequences, effectively silenced MYCN expression and induced apoptosis. This work provides a rational structure‑activity design strategy for tumor‑microenvironment‑responsive nucleic acid therapeutics and establishes a reference for further structural optimization.

Taken together, these results indicated that SAHA inhibition of FOXM1 oncogenic signaling may be mediated by MYCN in RB. Although the current data provide a preclinical rationale for the consideration of SAHA either as a single agent or in combination with other therapies, for the treatment of metastatic RB with MYCN-amplified RB1-/RB1-molecular phenotype, further research is warranted to gain greater insight into FOXM1-MYCN interaction in response to SAHA, in this molecular subtype of RB.

This study identifies ZRANB1 as an upstream deubiquitinase that stabilizes EZH2, thereby indirectly maintaining MYCN stability in MYCN-amplified neuroblastoma. These findings establish a ZRANB1-EZH2-MYCN regulatory axis and highlight ZRANB1 as a promising therapeutic target in MYCN-amplified NB.

The RUVBL proteins form a complex with ATPase activity that has broad cellular functions and we demonstrate that pharmacological inhibition of this protein complex results in a strong reduction of MYC(N) signaling, cell-cycle arrest, DNA damage, and apoptosis. We confirmed the association with MYCN and identified the RUVBL genes as independent prognostic biomarkers in human primary neuroblastoma data.

Understanding its complex biology is critical for the development of novel immunotherapies aimed at restoring effective anti-tumor immune responses, particularly in high-risk MYCN-amplified NB. Targeting the CCL2 axis represents a promising strategy to improve NB patient outcomes.

P2, N=94, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Mar 2026 --> Mar 2027 | Trial primary completion date: Mar 2026 --> Mar 2027

FD metrics derived from contrast-enhanced CT images are significantly associated with established clinical/pathological risk factors and overall survival in pediatric neuroblastoma. FD may serve as a non-invasive imaging biomarker to assist in risk stratification and clinical decision-making.