MYCN amplification

Finally, CMLD012824 led to growth inhibition in MYCN-amplified neuroblastoma models without generalized toxicity. Our studies highlight the key role of eIF4A1 in MYCN-amplified neuroblastoma and demonstrate the therapeutic potential of disrupting its function.

P=N/A, N=75, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Recruiting --> Active, not recruiting

P2, N=24, Completed, Fundació Sant Joan de Déu | Unknown status --> Completed

P2, N=42, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2023 --> Sep 2024

Overall, we identify a small group of genes highly enriched within functional gene categories related to mitotic processes that are commonly regulated by N-MYC, WDR5, and PDPK1 and suggest that a tripartite interaction between the three regulators may be responsible for setting the level of mitotic gene regulation in N-MYC amplified cell lines. This study provides a foundation for future studies to determine the exact mechanism by which N-MYC, WDR5, and PDPK1 converge on cell cycle related processes.

A retrospective analysis was performed on 104 pediatric patients with NB that had been confirmed by pathology...Post hoc analysis revealed the great potential of the M-model in differentiating MYCN gain from MNA (AUC 0.95, 95% CI: 0.89-1). The M-model model based on bio-omics and radiomics features is an effective tool to distinguish MYCN copy number category in pediatric patients with NB.

18 F-FDG-PET/CT is a valuable method for evaluating BMM in NB. The routine practice of performing a BMBA without discrimination may need to be reassessed. Negative result from 18 F-FDG-PET/CT could potentially spare children with invasive bone marrow biopsies.

P=N/A, N=186, Completed, Giselle Sholler | Active, not recruiting --> Completed | Trial completion date: Jun 2026 --> Jan 2024 | Trial primary completion date: Jun 2025 --> Jan 2024

Our results underscore the multifactorial nature of tumor aggressiveness in EPNs of the spinal region. This study enhances our knowledge of the clinical and pathological features of Sp-EPNs and MPEs and highlights the need for better diagnostic and prognostic markers in these rare tumors.

We propose that transcriptional subtyping may enhance precision prognosis and therapy stratification for patients with MYCN non-amplified neuroblastomas.

SESN1 functions as a new tumor suppressor gene via TLR signaling pathway in NB.

Furthermore, a short-term KDM4 inhibition in combination with conventional, cytotoxic chemotherapy results in complete tumor responses of xenografts with MNA. Thus, KDM4 blockade may serve as a transformative strategy to target the adrenergic CRC dependencies in MNA neuroblastomas.

P1, N=41, Active, not recruiting, Dana-Farber Cancer Institute | Recruiting --> Active, not recruiting | N=66 --> 41 | Trial completion date: Jun 2025 --> Jul 2024

We report the case of a baby boy with Rb and polydactyly exhibiting a 46, XY, 15pstk+ Karyotype. We discuss potential genetic factors related to both Rb and polydactyly. Furthermore, there is a need for further exploration into the impact of chromosomal polymorphisms in Rb with polydactyly.

P1, N=26, Active, not recruiting, Dana-Farber Cancer Institute | Trial completion date: Jan 2024 --> Jul 2024 | Trial primary completion date: Jan 2024 --> Jul 2024

The IDRFs are closely correlated with the MYCN amplification status and overall survival in neuroblastoma.

Moreover, silencing AF1q attenuated neuroblastoma tumorigenicity in vivo signifying AF1q's importance in neuroblastoma oncogenesis. Our findings reveal AF1q to be a novel regulator of N-Myc and potential therapeutic target in neuroblastoma.

To conclude, MYCN-amplified spinal ependymomas are rare tumors, accounting for ~ 4% of spinal cord ependymomas. Within the limitation of small sample size, MYCN IHC showed excellent concordance with MYCN gene amplification.

P=N/A, N=44, Completed, Masonic Cancer Center, University of Minnesota | Recruiting --> Completed | N=20 --> 44

Neuroblastoma with bilateral blindness is rare in the clinic, mostly in children of young age, and is often associated with MYCN amplification and multiple metastases. Early hormone shock therapy and optic nerve decompression are beneficial for preserving the child's vision. A joint multi-disciplinary treatment may help in the formulation of treatment decisions. Achieving a balance between good visual preservation and survival within the short optic nerve neurotherapeutic window is extremely challenging.

In conclusion, the inhibition of OCT4 binding at the MYCN locus resulted in reduced MYCN activity, which in turn led to the downregulation of high-ORF dominance transcripts and subsequently induced caspase-2-mediated cell death in MYCN-amplified NB cells. Therefore, disruption of the OCT4 binding at the MYCN locus may serve as an effective therapeutic strategy for MYCN-amplified NB.

Moreover, a synergistic effect between USP7 inhibitors and mTOR inhibitors was observed, suggesting the possibility of novel therapeutic strategies for cancer treatment. In conclusion, YCH2823 exhibits potential as an anticancer agent for the treatment of both TP53 wild-type and -mutant tumors.

P=N/A, N=600, Recruiting, Institut Curie | Trial primary completion date: Sep 2026 --> Apr 2027

P1, N=85, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Jan 2024 --> Jan 2025 | Trial primary completion date: Jan 2024 --> Jan 2025

Moreover, genetic knockdown of MTHFD1 or application of the anti-folic acid metabolism drug methotrexate (MTX) potentiated the anti-tumor effect of JQ1 both in vitro and in vivo. Taken together, MTHFD1 as an oncogene is a potential therapeutic target for MYCN-amplified NB. The combination of MTX with JQ1 is of important clinical translational significance for the treatment of patients with MYCN-amplified NB.

Our findings confirm the influence of CSC features in NB prognosis. The newly developed NB stemness-related four-gene signature prognostic signature could facilitate the prognostic prediction, and the identified hub genes may serve as promising targets for individualized treatments.

In addition, the administration of gomisin B over-regulated the expression of ESR1 protein in MYCN-amplified NB cells. In the present study, we investigated the potential pharmacological mechanisms of Aidi against NB and revealed the anti-NB effect of gomisin B, providing clinical evidence of Aidi in treating NB and establishing baselines for further research.

The most important breakpoints appear to be at 17q12 and 17q21. The former distinguishes between whole and partial chromosome 17q gain; the latter is a site of IGF2BP1 and NME1 genes that appear to be the main oncogenes responsible for the functional effects of 17q gain.

Therefore, predictive biomarkers have lagged behind the identification of prognostic biomarkers in CNS tumours. Emerging research from new clinical trials is cause for guarded optimism and may shift our conceptualisation of predictive biomarker testing in CNS tumours.

Exploiting this viral sensitivity to CD24 offers the possibility of its use as a prognostic target for a broad population of expressing cancers, many of which have shown resistance to current clinical therapies. Sensitivity to the tumoricidal effect of ZIKV on high-risk neuroblastoma tumors is dependent on CD24 expression, offering a prognostic marker for this oncolytic therapy in an extensive array of CD24-expressing cancers.

P2, N=153, Active, not recruiting, St. Jude Children's Research Hospital | Trial completion date: Dec 2023 --> Dec 2024

The prognosis of rhabdomyosarcoma, for example, primarily depends on histological and molecular characteristics. Advances in our understanding of clinically significant biomarkers will translate into more precise diagnoses, improved risk stratification and more effective and less toxic treatment in this challenging group of patients.

Our report adds to the rare number of cases in the literature of cerebellar HGGs in children. We recommend the use of both methylation array and TP53 screening in the differential diagnoses of poorly differentiated embryonal-like tumors of the cerebellum.

P1/2, N=120, Recruiting, National Cancer Institute (NCI) | Not yet recruiting --> Recruiting

Unexpectedly, her brain metastasis responded clinically, histologically, and by imaging to the treatment. We believe this is the first documented case of NBL of the brain responding to NAX.

P1/2, N=186, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Dec 2023 --> Dec 2025 | Trial primary completion date: Dec 2023 --> Dec 2025

P1, N=99, Active, not recruiting, Children's Oncology Group | Trial completion date: Sep 2023 --> Sep 2024

P1/2, N=135, Recruiting, Monte Rosa Therapeutics, Inc

These findings explain why single anti-PD-1/PD-L1 therapy may not be successful in NB, suggesting its combination with NK cell-adoptive cellular therapy as a promising strategy for relapsing/refractory NB. This study provides a potential prospect that patients with PD-L1-expressing NK cells may respond to anti-PD-1/PD-L1 therapy.

TERT was frequently placed in juxtaposition to a previously established gene in neuroblastoma tumorigenesis or cancer in general. Given the importance of high-risk neuroblastoma, means for mitigating active telomere maintenance must be therapeutically explored.

This approach to using copy number variation and immune receptor recombination read recovery levels to assess gene amplification and TIME, respectively, may be particularly efficient for the rapid evaluation of many other cancer types.

Surgical patients had shorter overall survival. However, the 2 patients with radiographic evidence of cord compression and acute neurological symptom onset who underwent initial, immediate surgery within 3 days of diagnosis had fewer long-term neurological deficits than surgical patients who underwent initial trials of chemotherapy. Thus, acute decompression may provide benefit in carefully selected patients with acute neurological deficits and cord compression on imaging.