MYCN amplification

Synergism between CAR T cells and the indirect MYCN inhibitor, MLN8237, was assessed in vitro using the Bliss model and in vivo in an immunocompromised mouse model...We identify target antigen downregulation as source of resistance against L1CAM-CAR T cells in MYCN-driven neuroblastoma cells. These data suggest that L1CAM-CAR T cell therapy combined with pharmacological MYCN inhibition may benefit patients with MYCN-amplified neuroblastoma.

Instead, response to induction chemotherapy modifies the effect of conventional prognostic factors. These data can help to further refine prognosis for patients with variable responses to induction and help to identify candidates who might benefit from treatment other than standard post-induction therapy.

Notably, the overexpression of FOXJ3 was associated with reduced cell density, proliferation, cells in S phase, colony-formation ability, transwell migration, neurosphere formation, spheroid diameter, and inhibition of AKT signaling in NB cells. Overall, these findings suggest that FOXJ3 functions as a novel tumor suppressor in NB, holding promise for potential therapeutic interventions.

We highlight the promising results of the clinical trial involving the combination of adavosertib and irinotecan, which encourages further clinical trials with adavosertib targeting NB with ATRX mutations. Preclinical results with BET inhibitors (OTX015 and AZD5153) and with 6-thio-2'-deoxyguanosine, targeting NB with TERT mutations, are promising. Both represent future therapeutic targets, emphasizing the need to prioritize research using these models.

This is the first reported case of IDEM double primary ependymoma and meningioma, highlighting the rarity of such cases and the importance of thorough diagnostic workup and surgical excision for IDEM tumors. Genetic analysis adds to the understanding of these rare tumors and guides management strategies.

HLB-0532259 surpasses the cellular efficacy of established allosteric Aurora-A inhibitors, exhibits favorable pharmacokinetic properties, and elicits tumor reduction in a murine xenograft NB model. This study broadly delineates a strategy for targeting "undruggable" proteins that are reliant on accessory proteins for cellular stabilization.

P1, N=99, Active, not recruiting, Children's Oncology Group | Trial completion date: Sep 2024 --> Sep 2025

CCL2 and N-Myc promote the viability of RA-treated cells, although the levels of these mediators were not consistently correlated with cellular outcomes, especially during apoptotic signaling.

P=N/A, N=600, Active, not recruiting, Institut Curie | Recruiting --> Active, not recruiting

It follows that alternating between inhibiting MDM2 to restore p53 activity and inhibiting ARF to attenuate p53 activity is a promising, if unorthodox, therapeutic strategy. The multicellular model has the advantages of modularity, high resolution, and scalability, making it a potential foundation for creating digital twins of neuroblastoma patients.

Molecular typing of pediatric spinal ependymomas aids in identifying very high-risk MYCN-amplified ependymomas. Further insights into the molecular heterogeneity of spinal ependymomas are needed for future clinical decision-making.

In summary, we established an in vitro model system to investigate the interaction of RB tumor cells with their TME. Our findings contribute to a better understanding of the relationship between RB tumor malignancy and its TME and will facilitate the development of effective treatment options for eye preserving therapies.