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BIOMARKER:

MYCN amplification

i
Other names: MYCN, MYCN Proto-Oncogene BHLH Transcription Factor, V-Myc Avian Myelocytomatosis Viral Oncogene Neuroblastoma Derived Homolog, Class E Basic Helix-Loop-Helix Protein 37, N-Myc Proto-Oncogene Protein, BHLHe37, NMYC, Neuroblastoma-Derived V-Myc Avian Myelocytomatosis Viral Related Oncogene, Neuroblastoma MYC Oncogene, Oncogene NMYC, BHLHE37, MODED, N-Myc, ODED
Entrez ID:
Related biomarkers:
1d
Finally, cross-species master regulator analysis identified FOXM1, together with additional hubs controlling transcriptome profiles of MYCN-driven neuroblastoma. In conclusion, time-resolved transcriptome analysis of early hyperplastic lesions and full-blown MYCN-driven neuroblastomas yielded novel components implicated in both tumor initiation and maintenance, providing putative novel drug targets for MYCN-driven neuroblastoma.
Journal
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • FOXM1 (Forkhead Box M1)
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MYCN amplification
11d
GRPR silencing significantly impaired mitochondrial oxygen consumption at baseline and during stress. In addition, GRPR regulates SHMT2, a key mitochondrial enzyme, at the post-transcriptional level. Therefore, SHMT2 and mitochondrial metabolism may play an important role in NB tumorigenesis.
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • AKT2 (V-akt murine thymoma viral oncogene homolog 2) • SHMT1 (Serine Hydroxymethyltransferase 1)
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MYCN amplification
17d
Together, our findings demonstrate synergistic efficacy of JQ1 or OTX-015 and temsirolimus against MYCN-driven NB, by dual-inhibition of MYCN (targeting transcription) and mTOR (targeting translation). Additional preclinical evaluation is warranted to determine the clinical utility of targeted therapy for high-risk NB patients.
Clinical • Journal
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • EIF4EBP1 (Eukaryotic translation initiation factor 4E binding protein 1) • BRD4 (Bromodomain Containing 4)
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MYCN amplification
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cisplatin • Torisel (temsirolimus) • JQ-1 • birabresib (OTX015)
20d
In a therapeutic setting, we showed that among six selected growth factors, EPO, and NGF showed the most pronounced protective effects in vitro against several promising anti-NB multikinase inhibitors: imatinib, dasatinib, crizotinib, cabozantinib, and axitinib...ERK inhibitors combined with anticancer drugs, especially with dasatinib, showed a synergistic effect on NB cell death. Consideration of growth factor signaling activity benefits NB outcome prediction and tailoring therapy regimens to treat NB.
Journal
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
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MYCN amplification
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Xalkori (crizotinib) • dasatinib • imatinib • Cabometyx (cabozantinib tablet) • Inlyta (axitinib)
20d
We conclude that evaluating the percentage of metastatic tumor tissue and tumor differentiation in BM biopsies is of clinical importance in the management of neuroblastoma patients.
Journal
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
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MYCN amplification
21d
Patients with HRNB frequently present with widely metastatic disease, with tumors harboring recurrent genetic aberrations (MYCN amplification, TERT rearrangements, and ATRX mutations), which are mutually exclusive and capable of promoting TMM. This review provides recent insights into our understanding of TMM in NB tumors, and highlights emerging therapeutic strategies as potential treatments for telomerase- and ALT-positive tumors.
Review • Journal
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • ATRX (ATRX Chromatin Remodeler)
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MYCN amplification • ATRX mutation • TERT amplification • TERT rearrangement
21d
The cone dedifferentiation in subtype 2 is associated with stemness features including low immune and interferon response, E2F and MYC/MYCN activation and a higher propensity for metastasis. The recognition of these two subtypes, one maintaining a cone-differentiated state, and the other, more aggressive, associated with cone dedifferentiation and expression of neuronal markers, opens up important biological and clinical perspectives for retinoblastomas.
Journal
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RB1 (RB Transcriptional Corepressor 1) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
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MYCN amplification
24d
In the presented work, we demonstrate that CAM assay (in ovo and ex ovo) can be simply employed to delineate the effects of cisplatin (CDDP) and ellipticine (Elli) on neuroblastoma (Nbl) cells in terms of their growth and metastatic potential...In in ovo CAM assay, both studied compounds (CDDP and Elli) exhibited significant (p < 0.001) inhibitory activity against extravasation to all investigated organs including distal CAM. Taken together, CAM assay could be a helpful and highly efficient in vivo approach for high-throughput screening of libraries of compounds with expected anticancer activities.
Journal
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
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MYCN amplification
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cisplatin
27d
This study analyzes the consequence of BORIS expression in neuroblastoma cells and thereby elucidate its downstream targets, which could help in designing effective therapeutic for treating neuroblastoma. Similar results were obtained in both MYCN amplified and non-MYCN neuroblastoma cell lines, indicating a common mechanism of BORIS/CTCFL action in neuroblastoma.
Journal
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • SMAD4 (SMAD family member 4) • SMAD3 (SMAD Family Member 3)
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MYCN amplification
29d
P1/2, N=374, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Recruiting --> Active, not recruiting | Trial completion date: May 2022 --> May 2023 | Trial primary completion date: May 2022 --> May 2023
Clinical • Enrollment closed • Trial completion date • Trial primary completion date • Combination therapy
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • FCGR3A (Fc Fragment Of IgG Receptor IIIa)
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MYCN amplification
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GD2-GD3 Vaccine
1m
Suboptimal doses of the CHK1 inhibitor MK-8776 plus the PARP inhibitor olaparib led to a MYCN-dependent accumulation of DNA damage and cell death in vitro and significantly reduced the growth of four in vivo models of MYCN-driven tumors, without major toxicities. Our data highlight the combination of PARP and CHK1 inhibitors as a new potential chemo-free strategy to treat MYCN-driven tumors, which might be promptly translated into clinical trials.
Journal • PARP Biomarker
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ATM (ATM serine/threonine kinase) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
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ATM mutation • MYCN amplification
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Lynparza (olaparib) • MK-8776
1m
Neuroblastoma patients attributed to high risk solely by MYCN amplification have generally a more favorable outcome. Mutations of genes of the RAS and/or p53 pathways and incomplete resection are the main risk factors predicting poor outcome.
Clinical • Journal
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
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TP53 mutation • MYCN amplification
1m
Unexpectedly, KO xenografts produced changes in plasma BChE similarly to WT tumors but lesser in magnitude. The disruption of BCHE locus in MYCN-amplified neuroblastoma cells decelerates proliferation and produces neuroblastoma cells that are less aggressive in female mice.
Preclinical • Journal
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ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
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MYCN amplification
1m
XPOT is identified as a novel prognostic predictor and potential therapeutic target for neuroblastoma patients. Further investigation should focus on the profound molecular mechanism underlying the tumor inhibition activity of XPOT inhibitors.
Journal
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
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MYCN amplification
1m
P1, N=45, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Aug 2021 --> Aug 2022 | Trial primary completion date: Aug 2021 --> Aug 2022
Clinical • Trial completion date • Trial primary completion date
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
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MYCN amplification
1m
Importantly, dipyridamole synergizes with DHODH inhibition to suppress neuroblastoma growth in animal models. These findings suggest that a combination of targeting DHODH and nucleoside transport is a promising strategy to overcome intrinsic resistance to DHODH-based cancer therapeutics.
Journal
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
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MYCN amplification
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dipyridamole
2ms
7/7 (100%) of MNA and 0/5 (0%) non-MNA cases were tested positive using ddPCR. Conclusions These results reflect the feasibility of ctDNA SCA profiling in molecular risk-stratification, with MNA status orthogonal conformation via ddPCR in a clinically relevant time frame, and suggest that ctDNA analysis could potentially reduce tissue requirements currently embedded in the management of NB.
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
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MYCN amplification
2ms
Conclusions Our study describes a specific, sensitive and fast MFC analysis allowing a precise quantification of i) BM tumor burden; ii) surface expression of GD2; iii) surface expression of different immune checkpoint ligands. MFC might usefully support other routinely used diagnostic and prognostic tools, improving diagnosis, prognosis, and orienting novel personalized treatments in patients with GD2 neg/low NB, who might benefit from innovative therapies combining B7-H3 targeting.
IO biomarker
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • CD276 (CD276 Molecule) • PTPRC (Protein Tyrosine Phosphatase Receptor Type C) • NCAM1 (Neural cell adhesion molecule 1)
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MYCN amplification
2ms
EORTC-QLQ-C30 scales were comparable to general population. With the limitation of non-randomization, no ch14.18-specific long-term sequelae could be identified.
Clinical • HEOR
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
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MYCN amplification
2ms
Conclusions The access to tumor cell-free DNA improves the diagnosis of genetic predisposition in case of conservative ocular therapy and provides access to biomarkers guiding the treatment strategy. The analysis of a gene panel is cost-effective and can be easily implemented in diagnostic laboratories.
RB1 (RB Transcriptional Corepressor 1) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
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MYCN amplification
2ms
Bone marrow is the most common site of metastasis in neuroblastomas. The status of metastatic disease in the bone marrow (BM) is a predictor of poor outcome. We conclude that evaluating the percentage of metastatic tumour tissue and tumour differentiation in bone marrow biopsies is of clinical importance in the management of neuroblastoma patients.
Clinical
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
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MYCN amplification
2ms
In the quest for new treatments, immunotherapy is poten- tially useful for chemotherapy-resistant disease. The inhibition of the programmed death ligand 1/programmed death 1 (PD-L1/PD-1) pathway has introduced a new era in cancer treatment.
PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
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PD-L1 expression • PD-L1 negative • MYCN amplification
2ms
Western blotting analysis with PARP and caspase-3 antibody support that BSAO/SPM treatment induces high levels of apoptosis in cells. The major conclusion is that BSAO/SPM treatment leads to antiproliferative and cytotoxic activity of both NB cell lines, associated with activation of apoptosis.
Journal • PARP Biomarker
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TP53 (Tumor protein P53) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • CASP3 (Caspase 3) • MIR34A (MicroRNA 34a-5p) • PARP1 (Poly(ADP-Ribose) Polymerase 1)
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MYCN amplification
2ms
Consequently, in a synchronous 9464D tumor model, CpG-PBNP-PTT induces complete tumor regression on the treated flank and significantly slows tumor progression on the untreated flank, improving animal survival. These findings demonstrate that localized administration of the CpG-PBNP-PTT nanoimmunotherapy drives potent systemic T cell responses in solid tumors such as NB and therefore has therapeutic implications for NB.
Journal • IO biomarker
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
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MYCN amplification
2ms
P1, N=68, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Aug 2021 --> Aug 2022 | Trial primary completion date: Aug 2021 --> Aug 2022
Clinical • Trial completion date • Trial primary completion date
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
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MYCN amplification
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Danyelza (naxitamab)
2ms
The protein expression of tumorigenic NMYC, Sox-2, Oct-4, FABP5, and HMGA1 significantly decreased 48 h post-drug treatment, whereas cleaved PARP1/caspase-3 and γH2AX increased 72 h post-drug treatment, compared with vehicle-treated cells in the MYCN-amplified IMR-32 cell line. We are the first to report this novel differential protein expression after ONC201 or ONC206 treatment in human neuroblastoma cells, demonstrating an important multitarget effect which may yield added therapeutic benefits in treating this devastating childhood cancer.
Journal • PARP Biomarker
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PDGFRB (Platelet Derived Growth Factor Receptor Beta) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • CASP3 (Caspase 3) • POU5F1 (POU Class 5 Homeobox 1) • SOX2 • EGF (Epidermal growth factor) • L1CAM (L1 cell adhesion molecule)
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MYCN amplification • POU5F1 expression
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ONC201 • ONC206
2ms
Persistently MIBG-avid metastatic lesions in subsets of patients following completion of therapy may not represent active disease that will progress. Further studies are needed to determine whether MYCN status or other biomarkers, and/or PET scans, may help identify patients with residual inactive MIBG lesions who require no further therapy.
Clinical • Journal
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
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MYCN amplification
2ms
P2, N=48, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Jun 2022 --> Jun 2023 | Trial primary completion date: Jun 2022 --> Jun 2023
Trial completion date • Trial primary completion date
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
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MYCN amplification
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temozolomide • irinotecan • Danyelza (naxitamab) • Leukine (sargramostim)
2ms
The HDAC inhibitors entinostat, romidepsin and vorinostat also increased TrkC in SH-SY5Y, Kelly and BE(2)-C but not IMR 32 cells. Moreover, NT-3 enhanced p75NTR/TrkC-T1 co-immunoprecipitation. The results indicate that VPA upregulates TrkC by activating epigenetic mechanisms and signaling pathways, and sensitizes neuroblastoma cells to NT-3-induced apoptosis.
Journal
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NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • SORT1 (Sortilin 1) • NGFR (Nerve Growth Factor Receptor) • RUNX3 (RUNX Family Transcription Factor 3) • EGR1 (Early Growth Response 1)
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MYCN amplification
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Zolinza (vorinostat) • entinostat (SNDX-275) • Istodax (romidepsin)
2ms
P2, N=132, Recruiting, Memorial Sloan Kettering Cancer Center | Not yet recruiting --> Recruiting
Enrollment open
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MYC (V-myc avian myelocytomatosis viral oncogene homolog) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • CSF2 (Colony stimulating factor 2)
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MYCN amplification
3ms
This illustrates an association of VIP-D with BRAF V600E mutations and demonstrates a therapeutic strategy in the specific context of VIP-D and BRAF V600E mutations in HR-NB patients. The addition of BRAF and MEK inhibitors allows continued conventional tumor-directed treatment by decreasing the severity of symptoms caused by this life-threatening complication.
Journal
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BRAF (B-raf proto-oncogene) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
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BRAF V600E • BRAF V600 • MYCN amplification
3ms
A revised 2021 COG neuroblastoma risk classifier (version 2) that uses the INRGSS and incorporates SCAs has been adopted to prospectively define COG clinical trial eligibility and treatment assignment.
Clinical • Journal
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
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MYCN amplification
3ms
Tumor volume reduction with neoadjuvant chemotherapy eliminates most IDRF in thoracic neurogenic tumors. Vascular IDRF are rapidly resolved at this site, making surgical resection and minimally invasive surgery possible.
Clinical • Journal
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
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MYCN amplification
3ms
Reestablishment of the activity of the clock activator RORα via its genetic overexpression and its stimulation through the agonist SR1078, restores BMAL1 expression and oscillation, effectively blocks MYCN-mediated tumor growth and de novo lipogenesis, and sensitizes NB tumors to conventional chemotherapy. In conclusion, reactivation of RORα could serve as a therapeutic strategy for MYCN-amplified NBs by blocking the dysregulation of molecular clock and cell metabolism mediated by MYCN.
Journal
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • ARNTL (Aryl Hydrocarbon Receptor Nuclear Translocator Like)
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MYCN amplification
3ms
These results demonstrate the feasibility of ctDNA profiling for molecular risk-stratification, and treatment monitoring in a clinically relevant time frame and the potential to reduce fresh tissue requirements currently embedded in the management of neuroblastoma.
Journal • Circulating tumor DNA
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
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MYCN amplification • ALK mutation
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Lorbrena (lorlatinib)
3ms
Our results indicate that tumors from children with high-risk neuroblastoma harboring a strong T cell-inflamed signature have a more favorable clinical outcome, and neoantigen load is a prognosis predictor, independent of T cell inflammation. Strategies to target SOX11 and other signaling pathways associated with non-T cell-inflamed tumors should be pursued as potential immune-potentiating interventions.
Journal • IO biomarker
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CD8 (cluster of differentiation 8) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • KMT2A (Lysine Methyltransferase 2A) • SOX11 (SRY-Box Transcription Factor 11)
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MYCN amplification
3ms
Clinical • Journal
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • H3F3A (H3 Histone Family Member 3A)
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MYCN amplification
3ms
miR-3140-3p efficiently downregulated MYCN expression by directly targeting the MAP3K3-ERK1/2 pathway in addition to BRD4 suppression, inhibiting tumor cell growth in BETi-acquired resistant NB cells. This study suggests that miR-3140-3p has the potential to overcome resistance to BETi in NB.
Preclinical • Journal
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • BRD4 (Bromodomain Containing 4)
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MYCN amplification
3ms
P1, N=44, Recruiting, Dana-Farber Cancer Institute | Trial primary completion date: Jun 2021 --> Dec 2021
Clinical • Trial primary completion date
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MYC (V-myc avian myelocytomatosis viral oncogene homolog) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
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MYCN amplification • MYC expression
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fimepinostat (CUDC-907)
3ms
IACS-010759 also suppressed tumor growth in zebrafish and mouse xenograft models of high-risk neuroblastoma. Together, these results demonstrate that DLST promotes neuroblastoma aggression and unveils OXPHOS as an essential contributor to high-risk neuroblastoma.
Journal
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
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MYCN amplification
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IACS-010759
3ms
The cases with positive c-MYC expression did not overlap those with MYCN amplification. Positive c-MYC expression portends a poor prognosis in patients with NTs.
Clinical • Journal
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MYC (V-myc avian myelocytomatosis viral oncogene homolog) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
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MYCN amplification • MYC expression • MYC positive
4ms
P1, N=15, Recruiting, Memorial Sloan Kettering Cancer Center
Clinical • New P1 trial
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
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MYCN amplification
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carboplatin • doxorubicin hydrochloride • ifosfamide • etoposide IV • vincristine • topotecan • mesna • cyclophosphamide intravenous
4ms
GSEA is a powerful approach to identify upregulated genes and potential therapeutic targets. Dinaciclib-AZD5153 combination therapy can be effective against MYCN-amplified and TERT-overexpressing neuroblastoma tumors.
Journal
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RB1 (RB Transcriptional Corepressor 1) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • TERT (Telomerase Reverse Transcriptase) • BRD4 (Bromodomain Containing 4)
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MYCN amplification • TERT amplification
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JQ-1 • dinaciclib (MK-7965) • AZD5153
4ms
Age related gene DST was an independent prognostic factor in MYCN non-amplified neuroblastoma. MYCN non-amplified younger neuroblastoma patients with higher DST expression levels had the best clinical overall survival.
Journal
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
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MYCN amplification
4ms
Clinical • New P2 trial • Combination therapy
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MYC (V-myc avian myelocytomatosis viral oncogene homolog) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • CSF2 (Colony stimulating factor 2)
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MYCN amplification
4ms
MIS was performed in limited cases of abdominal NB. A laparoscopic biopsy with careful attention to bleeding is feasible. The resected tumor size was shown to correlate with the patients' height. Tumor size within 6 cm of maximum diameter can be resected safely.
Clinical • Journal
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
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MYCN amplification
4ms
No difference in outcome was observed between rCOJEC and MSKCC-N5; however, acute toxicity was less with rCOJEC, and therefore rCOJEC is the preferred induction regimen for International Society of Pediatric Oncology European Neuroblastoma Group.
Clinical • Journal
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • IL2 (Interleukin 2)
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MYCN amplification
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cisplatin • carboplatin • etoposide IV • vincristine • melphalan • busulfan • Qarziba (dinutuximab beta) • isotretinoin oral
4ms
She was treated with targeted proton-beam radiation therapy. This is the fourth case of an intramedullary anaplastic myxopapillary ependymoma to date, and the first case in the cervical spine reported in the literature.
Clinical • Journal
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
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MYCN amplification
4ms
We further identified vincristine and rigosertib as a potential promising drug combination treatment. Our results show that rigosertib might be a useful therapeutic agent for MYCN-amplified neuroblastomas, especially in combination with existing agents.
Journal
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
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vincristine • Estybon (rigosertib)
4ms
These results indicate that MIAT is an upstream regulator of NMYC and that MIAT/NMYC axis disruption induces cell death in NMYC-amplified NBL cell lines. These findings reveal a novel mechanism for the regulation of NMYC in NBL, suggesting that MIAT might be a potential therapeutic target, especially for those with NMYC amplification.
Preclinical • Journal
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MYC (V-myc avian myelocytomatosis viral oncogene homolog) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
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MYCN amplification • MYC expression
4ms
Genetic alterations of ALK (clonal mutations and amplifications) in HR-NB are independent predictors of poorer survival. These data provide a rationale for integration of ALK inhibitors in upfront treatment of HR-NB with ALK alterations.
Journal
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ALK (Anaplastic lymphoma kinase) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
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MYCN amplification • ALK mutation • ALK amplification
4ms
The results indicated that chromosome 10 might be a new prognostic marker for NB. MYCN amplification and 1p36 deletion may be related to chromosome 10 abnormalities in NB. Additionally, NB patients with abnormal chromosome 10 were prone to orbital metastases.
Clinical • Journal
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
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MYCN amplification
4ms
The CT-based radiomics signature is able to predict MYCN amplification of pediatric abdominal NB with high accuracy based on SVM, Logistic and Random Forest classifiers, while Bayes classifier yields lower predictive performance. When combined with clinical and radiographic qualitative features, the clinics-radiomics nomogram can improve the performance of predicting MYCN amplification.
Clinical • Journal
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
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MYCN amplification
4ms
The stabilization of MYCN by FOXR2 represents an alternative mechanism to MYCN amplification to increase MYCN protein levels. As such, FOXR2 expression identifies another subset of neuroblastoma patients with unfavorable clinical outcome.
Clinical • Journal
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
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MYCN amplification
4ms
We treated both TP53-wild type and mutant, MYCN-amplified cell lines with the BETi JQ1 and the AURKAi Alisertib. BETi+AURKAi in MYCN-amplified NBL, particularly in the context of functional TP53, provided anti-tumor benefits in preclinical models. This combination should be studied more closely in a pediatric clinical trial.
Journal
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TP53 (Tumor protein P53) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • AURKA (Aurora kinase A)
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TP53 mutation • MYCN amplification
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JQ-1 • alisertib (MLN8237)
4ms
Testing of a paired ANNUBP precursor and MPNST in one patient demonstrated shared NF1 mutations but no PRC2 (SUZ12, EED) associated alterations. In summary, NGS has potential utility for robust characterization of nerve sheath tumors, and may represent a robust adjunct for diagnosis and clinical management.
Next-generation sequencing
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EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • CDKN2A (Cyclin-dependent kinase inhibitor 2A) • NF1 (Neurofibromin 1) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
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TP53 mutation • NF1 mutation • MYCN amplification
4ms
First, MDM2 inhibitor NVP-CGM097 increases the pro-death BH3-only protein NOXA to sensitize p53-wild-type, MYCN-amplified NBs to venetoclax. Second, the MCL-1 inhibitor S63845 sensitizes MYCN-amplified NB through neutralization of MCL-1, inducing synergistic cell killing when combined with venetoclax. Lastly, the standard of care drug cocktail cyclophosphamide and topotecan reduces the apoptotic threshold of NB, thus setting the stage for robust combination efficacy with venetoclax...Venetoclax is currently being evaluated in pediatric patients in the clinic, including neuroblastoma (NCT03236857). While establishment of safety is still ongoing, the data disclosed herein indicate rational and clinically actionable combination strategies that could potentiate the activity of venetoclax in MYCN-amplified NB patients.
Journal • IO biomarker
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BCL2 (B-cell CLL/lymphoma 2) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • PMAIP1 (Phorbol-12-Myristate-13-Acetate-Induced Protein 1)
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MYCN amplification
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Venclexta (venetoclax) • topotecan • S63845 • CGM097
5ms
P1/2, N=296, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: May 2021 --> May 2022 | Trial primary completion date: May 2021 --> May 2022
Clinical • Trial completion date • Trial primary completion date • Combination therapy
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • FCGR3A (Fc Fragment Of IgG Receptor IIIa)
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MYCN amplification
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GD2-GD3 Vaccine
5ms
While numerous pre-clinical data reported promising results with the use of combinatorial therapy that targets c-Met with other tumorigenic pathways, therapeutic resistance remains a problem, and long-term cures are rare. The possible mechanisms, including the overexpression and activation of compensatory tumorigenic mechanisms within the tumors or ineffective drug delivery methods that may contribute to therapeutic resistance observed in clinical trials are elaborated in this review.
Clinical • Review • Journal
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MET (MET proto-oncogene, receptor tyrosine kinase) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
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MYCN amplification
5ms
RNA-seq analysis of loss-of-function experiments of CASC15-003/NBAT1/MYCN/USP36 and JQ1-treated neuroblastoma cells uncovered MYCN-dependent oncogenic pathways...Functional experiments on one of the target genes, COL18A1, revealed its role in the NBAT1/CASC15-003-dependent cell adhesion feature in neuroblastoma cells. Our data show post-translational regulation of MYCN by NBAT1/CASC15-003/USP36, which represents a new regulatory layer in the complex multilayered gene regulatory network that controls MYCN expression.
Journal
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
|
JQ-1
5ms
The data gathered with CPI-203 were compared with the BRD4-degrading PROTAC A1874, used alone or in combination with the 14G2a mAb. Conclusion Research on combined targeting of GD2 and BRD4 in MYCN -amplified NB cells adds to efforts to pre-clinically evaluate new combined treatment approaches, aiming to improve survival of the high-risk neuroblastoma patients.
Preclinical
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • BRD4 (Bromodomain Containing 4)
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MYCN amplification
|
CPI-203
5ms
The data gathered with CPI-203 were compared with the BRD4-degrading PROTAC A1874, used alone or in combination with the 14G2a mAb. Conclusion Research on combined targeting of GD2 and BRD4 in MYCN -amplified NB cells adds to efforts to pre-clinically evaluate new combined treatment approaches, aiming to improve survival of the high-risk neuroblastoma patients.
Preclinical
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • BRD4 (Bromodomain Containing 4)
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MYCN amplification
|
CPI-203
5ms
The data gathered with CPI-203 were compared with the BRD4-degrading PROTAC A1874, used alone or in combination with the 14G2a mAb. Conclusion Research on combined targeting of GD2 and BRD4 in MYCN -amplified NB cells adds to efforts to pre-clinically evaluate new combined treatment approaches, aiming to improve survival of the high-risk neuroblastoma patients.
Preclinical
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • BRD4 (Bromodomain Containing 4)
|
MYCN amplification
|
CPI-203
5ms
The data gathered with CPI-203 were compared with the BRD4-degrading PROTAC A1874, used alone or in combination with the 14G2a mAb. Conclusion Research on combined targeting of GD2 and BRD4 in MYCN -amplified NB cells adds to efforts to pre-clinically evaluate new combined treatment approaches, aiming to improve survival of the high-risk neuroblastoma patients.
Preclinical
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • BRD4 (Bromodomain Containing 4)
|
MYCN amplification
|
CPI-203
5ms
IMR32 were xenografted in nude mice, which were treated with vehicle, olaparib (50 mg/kg), CHK inhibitor (CHK1i) MK-8776 (25 mg/kg) or their combination. Conclusion In conclusions, our data highlight a new potential chemo-free strategy to treat MNA NB. Moreover, they shed light on the involvement of ATM kinase in shaping NB cell responses to PARPi+CHK1i depending on their genetic background.
PARP Biomarker
|
ATM (ATM serine/threonine kinase) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • CHEK1 (Checkpoint kinase 1)
|
ATM mutation • Chr del(11q) • MYCN amplification
|
Lynparza (olaparib) • MK-8776
5ms
This effect could be due to the breast milk-mediated transfer of immune-complexes containing ALK, found in the milk of vaccinated mothers and in their offspring sera. Finally, maternal immunization against ALK induces a decrease in ALK expression in ALK-ECTM offspring tumor tissue Conclusion Overall, these results indicate that maternal immunization against ALK is able to induce an active immunization against this oncoantigen in the offspring, impairing tumor development and enhancing survival time in a preclinical model of high-risk NB
IO biomarker
|
ALK (Anaplastic lymphoma kinase) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
5ms
This effect could be due to the breast milk-mediated transfer of immune-complexes containing ALK, found in the milk of vaccinated mothers and in their offspring sera. Finally, maternal immunization against ALK induces a decrease in ALK expression in ALK-ECTM offspring tumor tissue Conclusion Overall, these results indicate that maternal immunization against ALK is able to induce an active immunization against this oncoantigen in the offspring, impairing tumor development and enhancing survival time in a preclinical model of high-risk NB
IO biomarker
|
ALK (Anaplastic lymphoma kinase) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
5ms
IMR32 were xenografted in nude mice, which were treated with vehicle, olaparib (50 mg/kg), CHK inhibitor (CHK1i) MK-8776 (25 mg/kg) or their combination. Conclusion In conclusions, our data highlight a new potential chemo-free strategy to treat MNA NB. Moreover, they shed light on the involvement of ATM kinase in shaping NB cell responses to PARPi+CHK1i depending on their genetic background.
PARP Biomarker
|
ATM (ATM serine/threonine kinase) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • CHEK1 (Checkpoint kinase 1)
|
ATM mutation • Chr del(11q) • MYCN amplification
|
Lynparza (olaparib) • MK-8776
5ms
This effect could be due to the breast milk-mediated transfer of immune-complexes containing ALK, found in the milk of vaccinated mothers and in their offspring sera. Finally, maternal immunization against ALK induces a decrease in ALK expression in ALK-ECTM offspring tumor tissue Conclusion Overall, these results indicate that maternal immunization against ALK is able to induce an active immunization against this oncoantigen in the offspring, impairing tumor development and enhancing survival time in a preclinical model of high-risk NB
IO biomarker
|
ALK (Anaplastic lymphoma kinase) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
5ms
This effect could be due to the breast milk-mediated transfer of immune-complexes containing ALK, found in the milk of vaccinated mothers and in their offspring sera. Finally, maternal immunization against ALK induces a decrease in ALK expression in ALK-ECTM offspring tumor tissue Conclusion Overall, these results indicate that maternal immunization against ALK is able to induce an active immunization against this oncoantigen in the offspring, impairing tumor development and enhancing survival time in a preclinical model of high-risk NB
IO biomarker
|
ALK (Anaplastic lymphoma kinase) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
5ms
IMR32 were xenografted in nude mice, which were treated with vehicle, olaparib (50 mg/kg), CHK inhibitor (CHK1i) MK-8776 (25 mg/kg) or their combination. Conclusion In conclusions, our data highlight a new potential chemo-free strategy to treat MNA NB. Moreover, they shed light on the involvement of ATM kinase in shaping NB cell responses to PARPi+CHK1i depending on their genetic background.
PARP Biomarker
|
ATM (ATM serine/threonine kinase) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • CHEK1 (Checkpoint kinase 1)
|
ATM mutation • Chr del(11q) • MYCN amplification
|
Lynparza (olaparib) • MK-8776
5ms
IMR32 were xenografted in nude mice, which were treated with vehicle, olaparib (50 mg/kg), CHK inhibitor (CHK1i) MK-8776 (25 mg/kg) or their combination. Conclusion In conclusions, our data highlight a new potential chemo-free strategy to treat MNA NB. Moreover, they shed light on the involvement of ATM kinase in shaping NB cell responses to PARPi+CHK1i depending on their genetic background.
PARP Biomarker
|
ATM (ATM serine/threonine kinase) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • CHEK1 (Checkpoint kinase 1)
|
ATM mutation • Chr del(11q) • MYCN amplification
|
Lynparza (olaparib) • MK-8776
5ms
In addition, inhibiting the thioredoxin, glutathione and peroxiredoxin pathways impairs cell viability of neuroblastoma cells. Conclusion In summary, we give an insight into the regulation of the antioxidant response in neuroblastoma by MYC proteins and we demonstrate that the inhibition of the antioxidant enzymes is a promising therapeutical strategy for neuroblastoma.
Clinical
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
5ms
In addition, inhibiting the thioredoxin, glutathione and peroxiredoxin pathways impairs cell viability of neuroblastoma cells. Conclusion In summary, we give an insight into the regulation of the antioxidant response in neuroblastoma by MYC proteins and we demonstrate that the inhibition of the antioxidant enzymes is a promising therapeutical strategy for neuroblastoma.
Clinical
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
5ms
In addition, inhibiting the thioredoxin, glutathione and peroxiredoxin pathways impairs cell viability of neuroblastoma cells. Conclusion In summary, we give an insight into the regulation of the antioxidant response in neuroblastoma by MYC proteins and we demonstrate that the inhibition of the antioxidant enzymes is a promising therapeutical strategy for neuroblastoma.
Clinical
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
5ms
In addition, inhibiting the thioredoxin, glutathione and peroxiredoxin pathways impairs cell viability of neuroblastoma cells. Conclusion In summary, we give an insight into the regulation of the antioxidant response in neuroblastoma by MYC proteins and we demonstrate that the inhibition of the antioxidant enzymes is a promising therapeutical strategy for neuroblastoma.
Clinical
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
5ms
Furthermore, transcription factor motifs for master regulators, including HNF1B, PAX3, and ZIC3, were significantly overrepresented in probes specific to distal regulatory regions in SP-MPEs. Our findings show substantial heterogeneity in pediatric SP-EPN and uncover novel enhancers and transcriptional pathways specific to the SP-MPE subgroup, providing a foundation for future therapeutic strategies.
Clinical • Journal
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
5ms
P1, N=14, Completed, Memorial Sloan Kettering Cancer Center | Active, not recruiting --> Completed | Trial completion date: Apr 2022 --> May 2021 | Trial primary completion date: Apr 2022 --> May 2021
Clinical • Trial completion • Trial completion date • Trial primary completion date
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
|
Danyelza (naxitamab)
5ms
P2, N=45, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jun 2021 --> Dec 2021 | Trial primary completion date: Jun 2021 --> Dec 2021
Clinical • Trial completion date • Trial primary completion date
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
|
cisplatin • carboplatin • doxorubicin hydrochloride • etoposide IV • vincristine • daunorubicin • topotecan • melphalan • Unituxin (dinutuximab) • thiotepa • Leukine (sargramostim) • cyclophosphamide intravenous • dexrazoxane • isotretinoin oral
5ms
Attempting to decipher how MYCN expression escapes elevated expression of inhibitory miRNAs, we present evidence that RNA-binding proteins like the IGF2 mRNA binding protein 1 reduce miRNA-directed downregulation of MYCN in neuroblastoma. Our findings emphasize the potency of post-transcriptional regulation of MYCN in neuroblastoma and unravel new avenues to pursue inhibition of this potent oncogene.
Journal
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • IGF2 (Insulin-like growth factor 2) • MIR17HG (MiR-17-92a-1 Cluster Host Gene) • MIR17 (MicroRNA 17)
|
MYCN amplification
5ms
P=N/A, N=20, Recruiting, Masonic Cancer Center, University of Minnesota | Trial primary completion date: Mar 2021 --> Mar 2022
Clinical • Trial primary completion date
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • CD34 (CD34 molecule)
|
MYCN amplification • LDH elevation
|
carboplatin • paclitaxel • ifosfamide • etoposide IV • melphalan • mesna • busulfan • thiotepa • ursodeoxycholic acid
5ms
Journal
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • CSF2 (Colony stimulating factor 2)
|
MYCN amplification
|
Danyelza (naxitamab) • Leukine (sargramostim)
5ms
Our results delineate a strategy for targeted epigenetic immunomodulation of high-risk NBs, whereby EHMT inhibitors alone or in combination with EZH2 inhibitors (in particular, MYCN-amplified NBs) could promote a T-cell-infiltrated TME via enhanced Th1-type chemokine expression.
Journal
|
EZH2 (Enhancer of zeste 2 polycomb repressive complex 2 subunit) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • IFNG (Interferon, gamma) • CXCL10 (Chemokine (C-X-C motif) ligand 10) • CXCL9 (Chemokine (C-X-C motif) ligand 9)
|
MYCN amplification • IFNG expression
5ms
Moreover, we found that MYCN fails to alter the general lipid metabolism and the amount of cystine imported by System X(-) for glutathione synthesis, both of which contribute to ferroptosis in alternative contexts. In conclusion, NB cells harboring MYCN amplification are prone to undergo ferroptosis conferred by TFRC upregulation, suggesting that GPX4-targeting ferroptosis inducers or TFRC agonists can be potential strategies in treating MYCN-amplified NB.
Journal
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • GPX4 (Glutathione Peroxidase 4)
|
MYCN amplification
5ms
The combination of CBL0137 and panobinostat is effective and well-tolerated in preclinical models of aggressive high-risk neuroblastoma, warranting further preclinical and clinical investigation in other pediatric cancers. Based on its potential to boost interferon and immune responses in cancer models, the drug combination holds promising potential for addition to immunotherapies.
Preclinical • Journal • Epigenetic controller
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
|
Farydak (panobinostat)
5ms
In sporadic cases with early diagnosis, Rbs with no RB1 pathogenic variant identified should be tested for MYCN. Conversely, tumors with MYCN should still be screened for RB1 pathogenic variants.
Journal
|
RB1 (RB Transcriptional Corepressor 1) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
5ms
CT-based radiomics is able to predict MYCN amplification status in NB, paving the way to the in-depth analysis of imaging based biomarkers that could enhance outcomes prediction.
Journal
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
5ms
Our results indicate that tumors from children with high-risk NBL harboring a strong Tinfl signature have a favorable clinical outcome, and neo is a prognosis predictor, independent of Tinfl. Strategies to target SOX11 and other signaling pathways associated with non-Tinfl tumors should be pursued as potential immune-potentiating interventions.
IO biomarker
|
CD8 (cluster of differentiation 8) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • KMT2A (Lysine Methyltransferase 2A) • SOX11 (SRY-Box Transcription Factor 11)
|
MYCN amplification
5ms
Our results indicate that tumors from children with high-risk NBL harboring a strong Tinfl signature have a favorable clinical outcome, and neo is a prognosis predictor, independent of Tinfl. Strategies to target SOX11 and other signaling pathways associated with non-Tinfl tumors should be pursued as potential immune-potentiating interventions.
IO biomarker
|
CD8 (cluster of differentiation 8) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • KMT2A (Lysine Methyltransferase 2A) • SOX11 (SRY-Box Transcription Factor 11)
|
MYCN amplification
5ms
Responsiveness correlates with MYCN expression, with MYCN-amplified cells being more susceptible to C646 treatment. Thus, exploiting the broad vulnerability of neuroblastoma cells to epigenetic targeting compounds represents an exciting strategy in neuroblastoma treatment, particularly for high-risk MYCN-amplified tumours.
Journal
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • CREBBP (CREB binding protein) • HDAC2 (Histone deacetylase 2)
|
MYCN amplification
6ms
P1/2, N=186, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Recruiting --> Active, not recruiting | Trial completion date: Dec 2021 --> Dec 2023 | Trial primary completion date: Dec 2021 --> Dec 2023
Enrollment closed • Trial completion date • Trial primary completion date • Combination therapy
|
MYC (V-myc avian myelocytomatosis viral oncogene homolog) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • CSF2 (Colony stimulating factor 2)
|
MYCN amplification
|
irinotecan • Danyelza (naxitamab)
6ms
These results could be important to consider when designing future clinical trials of ICI treatment in pediatric patients with relapsed or refractory solid tumors.
Journal • Checkpoint inhibition • PD(L)-1 Biomarker • IO biomarker
|
TP53 (Tumor protein P53) • CD8 (cluster of differentiation 8) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
TP53 mutation • MYCN amplification
6ms
These effects were lost in the GWAS cohort. We have demonstrated that the ODC1 G316A polymorphism has functional significance in neuroblastoma and is subject to allele-specific regulation by the MYCN oncoprotein.
Clinical • Journal
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
6ms
The interaction between MYCN-GA and ≤PR was significant (p = 0.006). Hence, the patients with MYCN-GA with non-remission status at HDC-autoSCR had a significantly poorer prognosis than the other subgroups, suggesting that HDC-autoSCR may be effective in patients with CR/VGPR regardless of MYCN gene status and in patients with MYCN-NGA regardless of remission status.
Clinical • Journal
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
6ms
P2, N=48, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Recruiting --> Active, not recruiting
Enrollment closed
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
|
temozolomide • irinotecan • Danyelza (naxitamab) • Leukine (sargramostim)
6ms
We describe a previously unrecognized mechanism of synthetic lethality between NXT1 and its paralog NXT2: their common essential binding partner NXF1 is lost only in the absence of both. We propose a potential therapeutic strategy for tumor-selective elimination of a protein that, if targeted directly, is expected to cause widespread toxicity.
Journal
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • NXF1 (Nuclear RNA Export Factor 1)
|
MYCN amplification
6ms
Despite partial response following combined sequential intravenous and intra-arterial chemotherapy, tumor relapse in the aqueous humor occurred with posterior chamber involvement over 360°, this transiently controlled by intracameral and intravitreal melphalan injections...FISH and SNP-array confirmed MYCN amplification. At 65 months follow-up the patient remained in good health without local recurrence or metastasis. To the best of our knowledge, this study is the first to attempt conservative management of an MYCN retinoblastoma, although secondary enucleation could not be avoided due to highly aggressive recurrence resisting all targeted modalities of chemotherapy.
Journal
|
RB1 (RB Transcriptional Corepressor 1) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification • RB1 mutation
|
melphalan
6ms
We present a suspected malignant transformation of a paravertebral mass from ganglioneuroblastoma to neuroblastoma after disease free survival of 5 years. This case raises the possibility of a dedifferentiating potential for ganglion cells in her nodular ganglioneuroblastoma of unfavorable type to neuroblastoma versus the presence of a long-term, quiescent form of neuroblastoma. If further cases are recognized, genetic analysis of the lesions might provide more insight into the molecular drivers of possible dedifferentiation into highly malignant neuroblastic tumors.
MYC (V-myc avian myelocytomatosis viral oncogene homolog) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification • MYC negative
6ms
Genomic sequencing for precision therapy was feasible both at diagnosis and relapse and identified genomic differences. Genomic analysis may identify novel treaments and subtypes which may be used to stratify patients and develop further understanding of relapse.
ALK (Anaplastic lymphoma kinase) • CDKN2A (Cyclin-dependent kinase inhibitor 2A) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • ATRX (ATRX Chromatin Remodeler) • PPM1D (Protein Phosphatase Mg2+/Mn2+ Dependent 1D) • SSX1 (SSX Family Member 1)
|
MYCN amplification • ALK mutation • ALK amplification
6ms
Our data suggests that USP7 inhibition may be a promising therapeutic strategy for children with high-risk and relapsed neuroblastoma.
PARP Biomarker
|
TP53 (Tumor protein P53) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • CASP3 (Caspase 3) • CASP7 (Caspase 7)
|
MYCN amplification • TP53 expression
6ms
The outcome of patients with stage 4(M) neuroblastoma aged less than 18 months is favorable when treated with high-risk or otherwise intensive therapy. The development of secondary malignancies and the potential of maturation to ganglioneuroma call for a controlled stepwise reduction of treatment intensity.
Clinical • Journal
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
6ms
National real-time CPR is feasible, delivering robust diagnostics to WHO criteria and assignment of clinical risk-status, significantly altering clinical management. Recommendations and experience from our study are applicable to advanced molecular diagnostics systems, both local and centralised, across rare tumour types, enabling their application in biomarker-driven routine diagnostics and clinical/research studies.
Journal
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • CTNNB1 (Catenin (cadherin-associated protein), beta 1)
|
MYCN amplification
6ms
Accuracy in clinical staging of the disease and assessment of the associated risks based on biological, clinical, surgical, and pathological criteria are of paramount importance for prognosis and to effectively plan therapeutic approaches. This review discusses the staging of NB and the biological and genetic features of the disease and several current therapies including targeted delivery of chemotherapy, novel radiation therapy, and immunotherapy for NB.
Review • Journal
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
6ms
Our study validates a sensitive MFC analysis providing information on GD2 and B7-H3 surface expression and allowing fast, specific and sensitive evaluation of BM tumor burden. With other routinely used diagnostic and prognostic tools, MFC can improve diagnosis, prognosis, orienting novel personalized treatments in patients with GD2low/neg NB, who might benefit from innovative therapies combining B7-H3 targeting.
Journal
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • CD276 (CD276 Molecule) • CD47 (CD47 Molecule)
|
MYCN amplification
6ms
Here, we demonstrate that down-regulation of IGF2BP1 activity, either by transcript silencing or chemical inhibition, suppresses neuroblastoma cell growth. Furthermore, the combination of IGF2BP1 inhibition along with commonly used chemotherapeutics that broadly affect DNA synthesis, or cyclin-dependent kinase (CDK) inhibitors that disrupt signal transduction, have a synergistic effect on the suppression of neuroblastoma cell proliferation.
Journal
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • IGF2 (Insulin-like growth factor 2)
|
MYCN amplification
6ms
Two eyes failed therapy and required enucleation; both had poor prognostic biomarkers (chromosome 6p gain or MYCN amplification) present in the AH at the time of diagnosis. In the context of previously established pre-analytical, analytical, and clinical validity, this provides evidence for larger, prospective studies to further establish the clinical utility of the AH liquid biopsy and its applications to precision oncology for RB.
Clinical • Journal • Liquid biopsy
|
RB1 (RB Transcriptional Corepressor 1) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
7ms
The thiotepa-melphalan high-dose therapy with thiotepa and melphalan may be effective for high-risk neuroblastoma. However, this regimen is toxic and warrants special attention in clinical practice.
Journal
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
|
melphalan • thiotepa
7ms
LDH, ferritin and the diagnostic I-mIBG scans significantly predicted mCR, but only LDH predicted 2-year overall survival. Ferritin and the modified Curie scores correlated with each other. MYCN amplification neither correlated with any aspect of the I-mIBG scans nor significantly predicted mCR or 2-year overall survival. LDH and ferritin are therefore appropriate neuroblastoma tumour markers to be used in low- and middle-income countries with limited or no access to mIBG scans and/or MYCN amplification studies.
Clinical • Journal
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
7ms
The therapeutic efficacy is due to both tumor cell-intrinsic and immune cell-mediated mechanisms. We propose that targeting the ability of Aurora-A to resolve transcription-replication conflicts is an effective therapy for MYCN-driven neuroblastoma (141 words).
Journal
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • AURKA (Aurora kinase A) • ATR (Ataxia telangiectasia and Rad3-related protein)
|
MYCN amplification
7ms
Clinical • Enrollment closed
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
|
cisplatin • doxorubicin hydrochloride • etoposide IV • vincristine • topotecan • melphalan • busulfan • Azedra (iobenguane I 131) • cyclophosphamide intravenous • isotretinoin oral • peripheral blood stem cell transplantation
7ms
We found that MYCN-amplified neuroblastoma is hypersensitive to the combination of an inhibitor of the lactate transporter MCT1, AZD3965, and complex I of the mitochondrion, phenformin...In mouse models of MYCN-amplified neuroblastoma, the combination was tolerable at concentrations where it shrank tumors and did not increase white-blood-cell toxicity compared to single drugs. Therefore, we demonstrate that a metabolic combination screen can identify vulnerabilities in subsets of cancer and put forth a metabolic combination therapy tailored for MYCN-amplified neuroblastoma that demonstrates efficacy and tolerability in vivo.
Journal • Combination therapy
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
|
AZD-3965
7ms
This study demonstrates that the Myc oncogene is an appropriate target for inducing tumor cell immunogenicity and suggests that Myc-suppressed whole tumor cells combined with checkpoint therapy could be used for formulating a personalized therapeutic tumor vaccine.
Journal
|
MYC (V-myc avian myelocytomatosis viral oncogene homolog) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
|
JQ-1
7ms
S/H staining pattern of MYCN protein overexpression by immunohistochemistry was associated with MYCN amplification, NH(+) and a poor prognosis. In contrast, the M/U staining pattern was associated with MYCN nonamplification and NH(-), and had no adverse prognostic effects for the 4SNB patients.
Clinical • Journal
|
MYC (V-myc avian myelocytomatosis viral oncogene homolog) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification • MYC overexpression • MYC expression
7ms
Finally, we showed that targeted inhibition of MYCN by BGA002 (anti-MYCN antigene PNA) is able to restore NK sensibility in MYCN-expressing NB cells. Overall, our study unveils a MYCN-driven immune network in NB and shows a therapeutic option to restore sensibility to immune cells.
Journal
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
|
BGA002
7ms
Taken together, our results highlight that: a) MAPK/ERK pathway is implicated in NB growth, and b) direct targeting of MAPK/ERK signaling pathway by using a novel small molecule MEK inhibitor inhibit NB proliferation and 3D tumor growth. We will further combine this MEK inhibitor with current chemotherapy drugs to develop effective therapeutic approaches for NB patients.
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • MAP2K2 (Mitogen-activated protein kinase kinase 2) • MAPK1 (Mitogen-activated protein kinase 1)
|
MYCN amplification
7ms
This study demonstrates that AH sampling at diagnosis is both feasible and safe. Molecular profiling of AH provides a plethora of diagnostic and prognostic information from only a single 0.1 mL AH sample.1
RB1 (RB Transcriptional Corepressor 1) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification • RB1 deletion
7ms
In conclusion, we present an in-depth characterization of the dynamic transcriptome profiles of TH-MYCN driven murine premalignant and established tumors and integrate with both primary human neuroblastoma tumor expression data, epigenetic and functional genomics data to identify and validate candidate cooperating dependencies suitable for targeting as a precision medicine approach in neuroblastoma.
Preclinical
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • FOXM1 (Forkhead Box M1)
|
MYCN amplification
7ms
A subset of neuroblastoma tumors that activate MYCN or MYC through hijacking of the HAND2 super-enhancer maintain high oncogene expression and are resistant to ATRA-mediated differentiation altogether. Thus, we provide mechanisms that account for the beneficial effects of retinoids against high-risk neuroblastoma and explain the rapid downregulation of expression of MYCN despite massive levels of gene amplification.
Clinical
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • MEIS1 (Meis Homeobox 1) • GATA3 (GATA binding protein 3) • SOX4 (SRY-Box Transcription Factor 4)
|
MYCN amplification
7ms
In turn, single cell ATAC-sequencing identified enrichment at chromatin-associated genes linked to transcription that were involved in processes, such as histone acetylation and at genes associated with core regulatory circuitries in NB. Collectively, these findings provide insights into cellular subtypes that undergo reconfiguration of the epigenome in NB by dysregulating gene expression and associated chromatin-gene expression loops.
ALK (Anaplastic lymphoma kinase) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • ATRX (ATRX Chromatin Remodeler)
|
TP53 mutation • MYCN amplification • ATRX mutation
7ms
Preliminary findings suggest that O-glycosylation is a barrier capable of limiting cellular uptake of agents in MYCN-amplified neuroblastoma cell lines. Ongoing studies are focused on investigating the influence of glycosylation inhibition on cytotoxicity of FDA-approved therapeutic agents.
IO biomarker
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification • MUC1 overexpression
7ms
Clinical • Enrollment open
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
|
Xalkori (crizotinib) • cisplatin • carboplatin • doxorubicin hydrochloride • etoposide IV • vincristine • topotecan • busulfan • Unituxin (dinutuximab) • thiotepa • Azedra (iobenguane I 131) • Leukine (sargramostim) • captisol-enabled melphalan • cyclophosphamide intravenous • dexrazoxane • isotretinoin oral
7ms
P1, N=14, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Apr 2021 --> Apr 2022 | Trial primary completion date: Apr 2021 --> Apr 2022
Clinical • Trial completion date • Trial primary completion date
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
|
Danyelza (naxitamab)
8ms
Importantly, the expression levels of genes involved in de novo fatty acid synthesis showed prognostic value for neuroblastoma patients. Our findings demonstrate that inhibition of de novo fatty acid synthesis is a promising pharmacological intervention strategy for the treatment of neuroblastoma independently of MYCN-status.
Clinical • Journal
|
MYC (V-myc avian myelocytomatosis viral oncogene homolog) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
8ms
Abnormal maintenance/elongation of telomeres; overexpression of telomerase reverse transcriptase (TERT) and the alternative lengthening of telomeres (ALT) phenotype due to ATRX mutation, are another molecular event in UH. The INPC, incorporating immunohistochemistry for MYCN, MYC, ALK, TERT and ATRX, represents a practical and implementable approach to create the biological category for the future management of patients with this unique disease.
Review • Journal
|
ALK (Anaplastic lymphoma kinase) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • TERT (Telomerase Reverse Transcriptase) • ATRX (ATRX Chromatin Remodeler)
|
MYCN amplification • ATRX mutation • MYC positive • TERT overexpression
8ms
We previously identified the first case of ALK F1174C-activating mutation in a patient with de novo NEPC who responded to the ALK inhibitor alectinib...These findings point to a role for ALK signaling in NEPC and the potential of co-targeting the ALK and Wnt/β-catenin pathways in ALK-driven tumors. Activated ALK and N-Myc are well known drivers in neuroblastoma development, suggesting potential similarities and opportunities to elucidate mechanisms and therapeutic targets in NEPC and vice versa.
Journal
|
ALK (Anaplastic lymphoma kinase) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification • ALK mutation • ALK F1174C
|
Alecensa (alectinib)
8ms
Tumor metabolic activity is higher in higher-stage MYCN-amplified neuroblastic tumors. Higher SUV and SUV were associated with worse overall survival but were not independent of other prognostic markers.
Clinical • Journal
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
8ms
P2, N=153, Active, not recruiting, St. Jude Children's Research Hospital | Trial completion date: Jul 2021 --> Dec 2023 | Trial primary completion date: Jan 2021 --> Dec 2021
Clinical • Trial completion date • Trial primary completion date
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • IL2 (Interleukin 2) • CSF2 (Colony stimulating factor 2)
|
MYCN amplification
|
cisplatin • doxorubicin hydrochloride • etoposide IV • vincristine • topotecan • melphalan • mesna • Proleukin (aldesleukin) • busulfan • Unituxin (dinutuximab) • Leukine (sargramostim) • Neupogen (filgrastim) • cyclophosphamide intravenous • humanised dinutuximab (Hu14.18K322A) • isotretinoin oral • levetiracetam
8ms
Analysis of expression profiles and the ultrastructure of zebrafish NB tumors with MYCN overexpression identified that GAS7 deficiency led to (i) downregulation of genes involved in cell-cell interaction, (ii) loss of contact among tumor cells as critical determinants of accelerated metastasis, and (iii) increased levels of MYCN protein. These results provide the first genetic evidence that GAS7 depletion is a critical early step in the cascade of events culminating in NB metastasis in the context of MYCN overexpression.
Journal
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • GAS7 (Growth Arrest Specific 7)
|
Chr del(17p) • MYCN amplification
8ms
It is present at diagnosis and is never acquired during later tumorigenesis of MYCN non-amplified neuroblastoma. This suggests that increased MYCN expression is an early event in these cancers leading to a peculiar dysregulation of cells that results in embryonal or cancer stem-like qualities, such as increased self-renewal, apoptotic resistance, and metabolic flexibility.
Review • Journal
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
8ms
What is New: • Infants with neuroblastoma achieve reasonable clinical outcome when treated with surgery with or without chemotherapy using a risk-stratified approach in China. • CNS metastasis in infants with neuroblastoma is very rare at diagnosis and had a worse prognosis than those without metastasis.
Clinical • Clinical data • Journal
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
8ms
However, we observed a significant up-regulation of p-L1CAM, MYCN and prohibitin, and significant down-regulation of Oct4, FABP5, HMGA1, p-ERK, cleaved/total caspase-3 and PARP1 in IMR-32 cells. HSP90 inhibition revealed a novel therapeutic mechanism of antitumor activity in MYCN-amplified neuroblastoma cells that may enhance therapeutic sensitivity.
Clinical • Journal • PARP Biomarker
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • CASP3 (Caspase 3) • POU5F1 (POU Class 5 Homeobox 1) • HSP90AA1 (Heat Shock Protein 90 Alpha Family Class A Member 1Heat Shock Protein 90 Alpha Family Class A Member 1)
|
MYCN amplification
8ms
In the present study, miRNA expression was analyzed in two human MYCN-amplified NB cell lines, one sensitive (HTLA-230) and one resistant to Etoposide (ER-HTLA), by microarray and RT-qPCR techniques...Principal component analysis data showed that the expression of miRNA-19b, -218, and -338 influenced metastases, and that the expression levels of all miRNAs analyzed were higher in therapy responders in respect to non-responders. Collectively, these findings suggest that these miRNAs might be involved in the regulation of the drug response, and could be employed for therapeutic purposes.
Journal
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
|
etoposide IV
8ms
P2, N=118, Recruiting, Giselle SaulnierSholler | Not yet recruiting --> Recruiting
Clinical • Enrollment open
|
TP53 (Tumor protein P53) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
TP53 mutation • MYCN amplification
8ms
SCAs were present in increasing frequencies according to stage and age: in 29% of localized tumors but in 92% of stage 4 tumors (p 12 months (p < 0.001). RAST successfully reduced chemotherapy exposure in low- and intermediate-risk patients with excellent long-term results while the outcome of high-risk disease met contemporary trials.
Journal
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
8ms
Further experimentation revealed that the elevated expression of miR‑17‑5p in SK‑N‑BE(2) cell‑derived exosomes significantly promoted the proliferative and migratory capacities of SH‑SY5Y cells by inhibiting PTEN. Collectively, these findings demonstrated that miR‑17‑5p derived from MYCN‑amplified NB cell exosomes promoted the migration and proliferation of non‑MYCN amplified cells, highlighting an exosome‑associated malignant role for miR‑17‑5p.
Journal
|
PTEN (Phosphatase and tensin homolog) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • MIR17 (MicroRNA 17)
|
MYCN amplification
9ms
We further defined master regulators at the single cell level and showed that MYCN is not constantly active or expressed within Kelly and BE2C cells, independently of cell cycle phase. The dataset, alongside a detailed and commented programming protocol to analyze it, is fully shared and reusable.
Preclinical • Journal
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • B2M (Beta-2-microglobulin) • GAPDH (Glyceraldehyde-3-Phosphate Dehydrogenase)
|
MYCN amplification
9ms
HDAC inhibitor, suberanoyl hydroxamic acid (SAHA), has shown clinical success in the treatment of cutaneous T-cell lymphoma but lacks efficacy as a single agent in many solid tumours, including neuroblastoma.First, we aimed to identify new compounds that potentiate SAHA activity and characterize their molecular mechanism...Repression of MYCN expression correlated with decreased USP5 protein and mRNA levels. Co-immunoprecipitation assays showed that USP5 and MYCN formed a protein complex.Taken together, our findings suggest that USP5 and MYCN participate in a forward feedback expression loop and that inhibition of USP5 function in neuroblastoma could be a novel therapeutic approach for MYCN-amplified tumours.
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
|
Zolinza (vorinostat)
9ms
Disruption of SNRPD3 in the presence of MYCN was sufficient to induce widespread mis-splicing that impact the cell cycle resulting in cell death. Our data suggests a role for PRMT5 inhibitors in the treatment of neuroblastoma and highlights SNRPD3 as a novel therapeutic vulnerability.
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • PRMT5 (Protein Arginine Methyltransferase 5)
|
MYCN amplification
9ms
A second mouse model with targeted disruption of Runx1t1 demonstrated that Runx1t1 haploinsufficiency is sufficient to prevent neuroblastoma development, while wild type mice remain completely healthy and fertile despite having only one functional copy of Runx1t1. Results will be presented showing that Runx1t1 forms part of a transcriptional co-repressor complex that regulates the epigenomic landscape as well as chromatin accessibility in neuroblastoma, to control cell fate pathway genes and maintain a de-differentiated state.
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • RUNX1T1 (RUNX1 Partner Transcriptional Co-Repressor 1)
|
MYCN amplification
9ms
P2, N=327, Completed, Memorial Sloan Kettering Cancer Center | Active, not recruiting --> Completed
Clinical • Trial completion • Minimal residual disease
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • CSF2 (Colony stimulating factor 2)
|
MYCN amplification
|
temozolomide • irinotecan • Leukine (sargramostim) • isotretinoin oral
9ms
TNB tumours have better outcomes than adrenal tumours. This may be due to varied factors reported here including non-metastatic disease at presentation, non-amplification of the MYCN oncogene and overall favourable molecular biology characteristics.
Clinical • Journal
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
9ms
In human neuroblastoma tissues, a high level of DDX21 expression correlated with a high level of N-Myc expression and with CEP55 expression, and independently predicted poor patient prognosis. Taken together, our data show that DDX21 induces CEP55 expression, MYCN-amplified neuroblastoma cell proliferation and tumorigenesis, and that DDX21 and CEP55 are valid therapeutic targets for the treatment of MYCN-amplified neuroblastoma.
Journal
|
MYC (V-myc avian myelocytomatosis viral oncogene homolog) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification • MYC expression
9ms
This reliance can be exploited through therapy with FDA-approved rheumatoid arthritis (RA) drugs sulfasalazine (SAS) and auranofin: in MYCN-amplified, patient-derived xenograft models, both therapies blocked growth and induced ferroptosis. SAS and auranofin activity was largely mitigated by the ferroptosis inhibitor ferrostatin-1, antioxidants like NAC, or by the iron scavenger deferoxamine (DFO). DFO reduced auranofin-induced ROS, further linking increased iron capture in MYCN-amplified NB to a therapeutic vulnerability to ROS-inducing drugs. These data uncover an oncogene vulnerability to ferroptosis caused by increased iron accumulation and subsequent reliance on the system Xc-/GSH pathway.
Journal
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • TFRC
|
MYCN amplification
|
Desferal (deferoxamine) • sulfasalazine
9ms
While some migrated tumor cells highly express CXCR4, cells of other origin do not. In the initial phase of migration, we determined a dominant role of AQP1 expression of migrating cells in the scratch assay.
Journal
|
CXCR4 (Chemokine (C-X-C motif) receptor 4) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • HIF1A (Hypoxia inducible factor 1, alpha subunit) • NCAM1 (Neural cell adhesion molecule 1)
|
MYCN amplification • HIF1A expression • NCAM1 expression
9ms
Neither the time of the cross-contamination event with IMR-32 is known nor was the final classification as a model for EFTs available with an associated STR profile. After a long road of errors and confusion, authentic CHP-100 is now characterized as a type II EWSR1-FLI1 fusion model 44?years after its establishment.
Journal
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • EWSR1 (EWS RNA Binding Protein 1) • FLI1 (Fli-1 Proto-Oncogene ETS Transcription Factor)
|
MYCN amplification • EWSR1-FLI1 fusion
9ms
Mechanistically, depleting any single Cullin did not fully recapitulate drug phenotypes, but sensitivity to SKP2 loss correlated with that of drug. Thus, intravitreal MLN4924 is a promising new retinoblastoma therapy, mimicking the cancer-specific lethality of eliminating SKP2 complexes.
Preclinical • Journal
|
RB1 (RB Transcriptional Corepressor 1) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • IL17RB (Interleukin 17 Receptor B)
|
MYCN amplification
|
pevonedistat (MLN4924)
9ms
ddPCR can be conducted more rapidly than FISH or Southern blotting. Accordingly, it should be useful for on-site clinical applications aimed at detecting CNAs in NB and performing risk stratification promptly after diagnosis.
Journal
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
Chr del(11q) • MYCN amplification
9ms
FISH is a useful diagnostic tool for evaluating high-risk NBLs in which TERT-PR rearrangements have occurred.
Journal
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • TERT (Telomerase Reverse Transcriptase)
|
MYCN amplification
9ms
Our study demonstrates that vesicles released from irradiated neuroblastoma cells stimulate proliferation and invasiveness that correlate with the epithelial to mesenchymal transition in non-irradiated cells. Moreover, our results suggest that, at least in neuroblastomas, targeting the extracellular vesicles may represent a novel therapeutic approach to counteract the side effects associated with radiotherapy.
Journal
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
9ms
B02 further synergized with clinically relevant topotecan (TPT) to engage this pathway, activating p53-BAX mediated killing of RB but not human retinal progenitor cells. Deleting p21 or applying the BCL2/BCL2L1 inhibitor Navitoclax re-engaged the p53-BAX axis, and synergized with B02, TPT or both to override resistance. These data expose new synergistic therapies to trigger p53-induced killing in diverse RB subtypes.
Journal
|
BRCA1 (Breast cancer 1, early onset) • BCL2 (B-cell CLL/lymphoma 2) • RB1 (RB Transcriptional Corepressor 1) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • BCL2L1 (BCL2-like 1) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • CHEK1 (Checkpoint kinase 1)
|
MYCN amplification
|
topotecan • navitoclax (ABT 263)
9ms
Neuroblastoma cells with c-MYC overexpression also required ABCE1 to maintain cell proliferation and translation. Taken together, ABCE1-mediated translation constitutes a critical process in the progression of N-MYC-driven and c-MYC-driven cancers that warrants investigations into methods of its therapeutic inhibition.
Journal
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification • MYC overexpression • MYC expression
9ms
TAS-119 inhibited TRK-fusion protein activity and exhibited robust growth inhibition of tumor cells via a deregulated TRK pathway in vitro and in vivo. Our study indicates the potential of TAS-119 as an anticancer drug, especially for patients harboring MYC amplification, CTNNB1 mutation, and NTRK fusion.
Preclinical • Journal
|
NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • AURKA (Aurora kinase A) • AURKB (Aurora Kinase B) • NTRK (Neurotrophic receptor tyrosine kinase)
|
MYCN amplification • CTNNB1 mutation • NTRK fusion
|
VIC-1911
9ms
DNA methylation and demethylation are mediated by DNA methyltransferases (DNMTs) and ten-eleven translocation (TET) proteins, respectively, while histone modifications are coordinated by histone acetyltransferases and deacetylases (HATs, HDACs), and histone methyltransferases and demethylases (HMTs, HDMs). This article focuses predominately on the crosstalk between the epigenome and NB, and the implications it has on disease diagnosis and treatment.
Review • Journal
|
ALK (Anaplastic lymphoma kinase) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • ATRX (ATRX Chromatin Remodeler)
|
TP53 mutation • MYCN amplification
9ms
Statin sensitivity was driven by HMGCR expression, the rate-limiting enzyme for cholesterol synthesis, which correlated with statin sensitivity across NBL cell lines, thus providing a drug sensitivity biomarker. Comparing expression profiles from sensitive and resistant cell lines revealed a TGFBR2 signaling axis that regulates HMGCR, defining an actionable addiction in that leads to MESN-subtype-dependent apoptotic cell death.
Journal
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
|
lovastatin
9ms
Clinical • New P2 trial
|
TP53 (Tumor protein P53) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
TP53 mutation • MYCN amplification
9ms
The RIST treatment protocol has a multimodal metronomic therapy design combining molecular-targeted drugs (Rapamycin and Dasatinib) with chemotherapy backbone (Irinotecan and Temozolomide), which is currently verified in a phase II clinical trial (NCT01467986)...By comparing the IC values of Torin-1, Torin-2, AZD3147 and PP242 we established that only Torin-2 inhibited cell viability of all three MycN-amplified neuroblastoma cell lines tested at nanomolar concentration...However, at this point we cannot rule out that Torin-2 has increased toxicity due to its potency in more complex systems. Nonetheless, our results suggest that including Torin-2 as a substitute for Rapamycin in the RIST protocol may represent a valid option to be evaluated in prospective clinical trials for relapsed or treatment-refractory high-risk neuroblastoma.
Journal
|
CCND1 (Cyclin D1) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification • CCND1 expression
|
dasatinib • temozolomide • irinotecan • sirolimus • Torin1 • torkinib (PP242)
9ms
Clinical • Enrollment closed
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
|
Xalkori (crizotinib) • cisplatin • carboplatin • doxorubicin hydrochloride • etoposide IV • vincristine • topotecan • busulfan • Unituxin (dinutuximab) • thiotepa • Azedra (iobenguane I 131) • Leukine (sargramostim) • captisol-enabled melphalan • cyclophosphamide intravenous • dexrazoxane • isotretinoin oral
10ms
MYCN and TP53 were hub genes in PeC. MYCN and FAK amplification was also detected and analyzed, and the findings indicated that these two genes are predictors of poor prognosis in PeC.
Journal
|
TP53 (Tumor protein P53) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • MDM2 (E3 ubiquitin protein ligase) • BMI1 (BMI1 proto-oncogene, polycomb ring finger) • NTRK (Neurotrophic receptor tyrosine kinase)
|
TP53 deletion • MYCN amplification
10ms
Investigation of Math1-creER::Brg1::lslMYCN mice with a tamoxifen induction at postnatal day 3 revealed a regular survival but significant increase in cerebellar granule neuron precursor proliferation, followed by a delayed inward migration of these cells...Our results indicate a time-specific function of Brg1 in cerebellar granule neuron precursors. Yet, the exact temporal and spatial origin of non-WNT/non-SHH MB remains unclear.
Journal
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4)
|
MYCN amplification
|
tamoxifen
10ms
Despite the poor prognosis in cases of disseminated skeletal involvement and N-myc amplification, the young patient remained free of recurrence during a follow-up period of 36 months after multidisciplinary treatment. The purpose of this case report is to increase awareness of the clinical features of neuroblastoma among pediatric dentists to support early-stage diagnosis and highlight interdisciplinary management.
Journal
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
10ms
Clinical • Journal
|
TP53 (Tumor protein P53) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
10ms
The literature review revealed that neuroblastoma cell lines containing upregulation of the protooncogene MYCN were found to be less responsive to treatment. In MYCN-amplified cells, there was a relationship with increased glycan expression. These cell lines had greater expression of the enzyme C2GNT1, responsible for adding a glucose derivative creating the Core 2 Structure of O-glycans.
Preclinical
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
10ms
Clinical • Enrollment open • Combination therapy
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
|
temozolomide • irinotecan • Unituxin (dinutuximab) • Leukine (sargramostim) • isotretinoin oral
10ms
When tested with standard-of-care cytotoxics at human Cmax-equivalent concentrations, MYCN and non-MYCN amplified PDCs showed differential response to cyclophosphamide and topotecan, which mirrored the corresponding patients' responses, and correlated with gene signatures of chemosensitivity. In this translational proof-of-concept, early-phase neuroblastoma PDCs enriched for the mesenchymal cell subpopulation recapitulated individual molecular and phenotypic profile of patient tumors, and highlights their potential as a platform for individualized ex-vivo drug response testing.
Journal • Gene Signature
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
Chr del(11q) • MYCN amplification
|
topotecan • cyclophosphamide intravenous
10ms
Clinical • New P3 trial
|
TP53 (Tumor protein P53) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
TP53 mutation • MYCN amplification
|
cisplatin • carboplatin • temozolomide • vincristine • lomustine • thiotepa
10ms
MP1 was stable under storage and laboratory handling conditions. The validated method was successfully applied to assess the solubility, in-vitro metabolism, plasma protein binding, and bio-distribution studies of MP1.
Journal
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
10ms
These results suggest that NORAD may serve as a tumor suppressor in NB pathogenesis and progression. Thus, NORAD is a potential therapeutic target and a promising prognostic marker for NB patients.
Journal • PARP Biomarker
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • PARP1 (Poly(ADP-Ribose) Polymerase 1)
|
MYCN amplification
10ms
The risk of CNS recurrence is linked to both patient and disease characteristics, with neither impact of HDC nor immunotherapy. These findings support the current treatment strategy and do not justify a CNS prophylactic treatment.
Journal
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
10ms
The presence of IDRFs at diagnosis was associated with high-risk clinical, molecular, and histopathologic features of neuroblastoma. The IDRF group tumor infiltration into adjacent organs and structures was associated with decreased survival. Collectively, these findings may assist surgical planning and medical management for neuroblastoma patients.
Clinical • Journal
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
10ms
Comprehensive NGS analysis reliably detects relevant mutations, amplifications, and chromosomal copy number changes in retinoblastoma. The presence of genetic alterations beyond RB1 inactivation correlates with aggressive histopathologic features.
Journal
|
ARID1A (AT-rich interaction domain 1A) • RB1 (RB Transcriptional Corepressor 1) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • ATRX (ATRX Chromatin Remodeler) • RAF1 (Raf-1 Proto-Oncogene Serine/Threonine Kinase) • MDM4 (The mouse double minute 4) • FAT1 (FAT atypical cadherin 1)
|
ARID1A mutation • MYCN amplification • RB1 mutation • RB1 deletion
10ms
Gross total resection of cervicothoracic and apical thoracic neuroblastoma can be accomplished by TAT with minimal morbidity.
Clinical • Journal
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
10ms
The ability of FLM to penetrate tumor cells, transporting the encapsulated drugs, substantially improved the therapeutic efficiency of this system. Moreover, the enhancement of GD2 expression in FLM treated tumors offers the possibility to further increase the antitumor effect by the use of anti-GD2 CAR-T cells and anti-GD2 antibodies in combination with FLM in multimodal therapies.
Journal
|
NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
|
Revlimid (lenalidomide)
10ms
HSCT can improve the prognosis of patients with bone or bone marrow metastasis. It can also retard the time of progression or recurrence for patients with MYCN amplification.
Clinical • Retrospective data • Journal
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
10ms
P2, N=59, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Recruiting --> Active, not recruiting
Clinical • Enrollment closed
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
|
Danyelza (naxitamab) • isotretinoin oral
10ms
However, combining a PHGDH inhibitor with the standard-of-care chemotherapy drug, cisplatin, revealed antagonism of chemotherapy efficacy in vivo...Altogether, PHGDH knockout or inhibition by small molecules consistently slows proliferation, but stops short of killing the cells, which then establish resistance to classical chemotherapy. Although PHGDH inhibition with small molecules has produced encouraging results in other preclinical cancer models, this approach has limited attractiveness for patients with neuroblastoma.
Clinical • Journal
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
|
cisplatin
10ms
MYCNOS1 silencing enhanced the response of retinoblastoma cells to topotecan but not carboplatin. MYCNOS1 supports progression of retinoblastoma. Inhibition of MYCNOS1 expression may be necessary to suppress MYCN activity when treating MYCN-amplified cancers without RB1 mutation.
Journal
|
RB1 (RB Transcriptional Corepressor 1) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification • RB1 mutation
|
carboplatin • topotecan
11ms
AZD2014 treatment failed however to inhibit mTOR signalling in vivo and did not significantly modulate intratumoural NET-1 activity. Image analysis of F-mFBG PET data showed correlation to tumour NET-1 protein expression, while further studies are needed to elucidate whether NET-1 upregulation induced by blocking mTOR might be a useful adjunct to I-mIBG therapy.
Journal
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
|
vistusertib (AZD2014)
11ms
P=N/A, N=7, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Nov 2020 --> Nov 2021 | Trial primary completion date: Nov 2020 --> Nov 2021
Clinical • Trial completion date • Trial primary completion date
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
|
Danyelza (naxitamab)
11ms
Despite benefits from standard anti-GD2 immunotherapy in high-risk NB patients, those with 11q deletion still face poor outcome. This NB subgroup displays intratumoral immune suppression profiles, revealing a potential therapeutic strategy with combination immunotherapy to circumvent this immune checkpoint blockade.
Journal • PD(L)-1 Biomarker
|
PD-L1 (Programmed death ligand 1) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • IDO1 (Indoleamine 2,3-dioxygenase 1) • TGFB1 (Transforming Growth Factor Beta 1) • IL10 (Interleukin 10)
|
PD-L1 expression • Chr del(11q) • MYCN amplification
11ms
Different cell response to hypoxia can be mediated by TG2 isoforms in function of MYCN amplification status. A better understanding of the role of TG2 isoforms in neuroblastoma may open new venues in a diagnostic and therapeutic perspective.
Journal
|
CCND1 (Cyclin D1) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
11ms
The second class of MYCN amplicons is characterized by high structural complexity, lacks key local enhancers, and instead contains distal chromosomal fragments harboring CRC-driven enhancers. Thus, ectopic enhancer hijacking can compensate for the loss of local gene regulatory elements and explains a large component of the structural diversity observed in MYCN amplification.
Journal
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
11ms
MCT1 inhibition was highly synergistic with vincristine and LDHA inhibition under cell culture conditions, but this combination was ineffective against neuroblastoma xenografts...Co-treatment of neuroblastoma cells with inhibitors of MCT1 and LDHA, the enzyme responsible for lactate production, resulted in a large increase in intracellular pyruvate and was highly synergistic in decreasing neuroblastoma cell viability. These results highlight the potential of targeting MCT1 in neuroblastoma in conjunction with strategies that involve disruption of pyruvate homeostasis and indicate possible resistance mechanisms.
Journal
|
LDHA (Lactate dehydrogenase A) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • HIF1A (Hypoxia inducible factor 1, alpha subunit) • MCT1 (SLC16A1)
|
MYCN amplification
|
vincristine
11ms
A positive CNL genomic background was associated with worse outcome in patients with heterogeneous MYCN amplification (22.5% survival probability, P < 0.05). We conclude that characterizing a tumor genomic background according to predominance of genome gained or lost contributes toward improved outcome prediction and brings greater insight into the tumor biology of HR-NB patients.
Clinical • Journal
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
11ms
P=N/A, N=184, Active, not recruiting, Giselle SaulnierSholler | Trial completion date: Jun 2021 --> Jun 2026 | Trial primary completion date: Jun 2020 --> Jun 2025
Clinical • Trial completion date • Trial primary completion date
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
11ms
This study provides novel insights into the genomic background of MYCN non-amplified NB. Activation of immune-related pathways in the high-risk group and the results of TMB and mutational signature analyses collectively suggest the need for further investigation to discover potential immunotherapeutic strategies for NB.
Journal • Tumor Mutational Burden
|
TMB (Tumor Mutational Burden) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • MUC16 (Mucin 16, Cell Surface Associated)
|
TMB-H • MYCN amplification
11ms
Multivariate analysis identified histological type (p = 0.026), metastasis (p = 0.031) and KMT2C mutational status (p = 0.046) as independent prognosticators in our cohort. In summary, we identified distinct clinical and mutational characteristics of adult medulloblastomas that will inform their risk stratification and treatment.
Clinical • Journal
|
TP53 (Tumor protein P53) • NOTCH1 (Notch 1) • PTCH1 (Patched 1) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • KMT2D (Lysine Methyltransferase 2D) • TERT (Telomerase Reverse Transcriptase) • KMT2C (Lysine Methyltransferase 2C) • SMO (Smoothened Frizzled Class Receptor) • SUFU (SUFU Negative Regulator Of Hedgehog Signaling)
|
TP53 mutation • MYCN amplification • KMT2C mutation • PTCH1 mutation • SUFU mutation
11ms
Pineal parenchymal tumors are rare and can be difficult to diagnose. Therefore, elucidation of characteristic genetic alterations will be useful for neuropathologists, especially for low grade pineal parenchymal tumors. We report here the first single nucleotide variants in pineocytoma, and novel genomic alterations in PPTID and pineoblastoma.
PALB2 (Partner and localizer of BRCA2) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • RAD51B (RAD51 Paralog B) • AKT2 (V-akt murine thymoma viral oncogene homolog 2) • DICER1 (Dicer 1 Ribonuclease III)
|
MYCN amplification
11ms
Our NGS panel-based CNV analysis detects neuroblastoma relevant genomic alterations with high fidelity. The NGS panel alone would be sufficient for the detection of clinically relevant CNVs and sequence variants in the majority of neuroblastoma cases, despite its higher tumor percentage requirement compared to WGA.
ALK (Anaplastic lymphoma kinase) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
11ms
Gain of MYCN or GNAS in ARMS, impaired cell cycle/TP53 pathways, biallelic loss of NF1, and WNT pathway defects in ERMS, as well as germline mutations are associated with poor survival in patients with RMS. Our data show that genomic alterations should be evaluated for incorporation into risk classifiers for pediatric RMS.
Clinical • Clinical data
|
ALK (Anaplastic lymphoma kinase) • FGFR1 (Fibroblast growth factor receptor 1) • CDKN2A (Cyclin-dependent kinase inhibitor 2A) • ARID1A (AT-rich interaction domain 1A) • NF1 (Neurofibromin 1) • PTCH1 (Patched 1) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • CDK4 (Cyclin-dependent kinase 4) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • MDM4 (The mouse double minute 4) • FOXO1 (Forkhead box O1) • GNAS (GNAS Complex Locus) • DICER1 (Dicer 1 Ribonuclease III)
|
TP53 mutation • HER-2 mutation • NF1 mutation • MYCN amplification • PTCH1 mutation • CTNNB1 mutation
11ms
Although neuroblastomas with heterogeneous MNA demonstrate significantly different biological and clinical patterns compared with homogeneous MNA, prognosis is similar between the two groups. These results support current practice that treats patients with heterogeneous MNA similarly to patients with homogeneous MNA.
Clinical • Journal
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
11ms
P1, N=45, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Aug 2020 --> Aug 2021 | Trial primary completion date: Aug 2020 --> Aug 2021
Clinical • Trial completion date • Trial primary completion date
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
12ms
Signature 18 is enriched in neuroblastomas with MYCN amplification, 17q gain, and increased expression of mitochondrial ribosome and electron transport-associated genes. Recurrent FGFR1 variants in six patients, and ALK N-terminal structural alterations in five samples, identify additional patients potentially amenable to precision therapy.
Journal
|
ALK (Anaplastic lymphoma kinase) • FGFR1 (Fibroblast growth factor receptor 1) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • ATRX (ATRX Chromatin Remodeler)
|
MYCN amplification • ATRX mutation
12ms
Finally, we show with H3K27Ac ChIP-Seq that these cell lines retain expression of key neuroblastoma super-enhancers (SE). We anticipate this dataset, coupled with available transcriptomic profiling on the same cell lines, will enable the discovery of novel gene regulatory mechanisms in neuroblastoma.
Journal
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
12ms
• A CT-based radiomics signature has the ability to predict MYCN amplification (MNA) in neuroblastoma. • Both pre- and post-contrast CT images are valuable in predicting MNA. • Associating the radiomics signature with clinical factors improved the predictive performance of MNA, compared with clinical model alone.
Clinical • Journal
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
12ms
Focus on heterogeneous intratumor segmental chromosome aberrations and mutations, as a mirror image of tumor microenvironment, is a vital area of future research.
Preclinical • Journal
|
ALK (Anaplastic lymphoma kinase) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification • ALK mutation
12ms
Th- I-MIBG administered shortly before HD-BuMel is a safe and effective regimen for patients with advanced MIBG-avid NB. These patients should be managed in centers with proven expertise.
Journal
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
|
melphalan • busulfan • Defitelio (defibrotide)
12ms
Moreover, we have identified several novel mechanisms of PI3KAKT treatment resistance and are currently identifying therapies that may overcome this resistance through RNA seq analysis. In summary, well defined genetic drivers of GBM can lead to informed mouse model generation to test promising therapies.
TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • SOX2
|
MYCN amplification • TP53 expression
12ms
P3, N=3300, Recruiting, St. Anna Kinderkrebsforschung | Trial completion date: Sep 2024 --> Sep 2026 | Trial primary completion date: Nov 2019 --> Sep 2021
Trial completion date • Trial primary completion date
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • IL2 (Interleukin 2)
|
MYCN amplification
|
cisplatin • carboplatin • doxorubicin hydrochloride • etoposide IV • vincristine • melphalan • Proleukin (aldesleukin) • busulfan • Qarziba (dinutuximab beta) • Neupogen (filgrastim) • cyclophosphamide intravenous
12ms
P2, N=62, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Jun 2021 --> Jun 2022 | Trial primary completion date: Jun 2021 --> Jun 2022
Trial completion date • Trial primary completion date
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
|
temozolomide • irinotecan • Danyelza (naxitamab) • Leukine (sargramostim)
12ms
Extracellular vesicles (EVs) released by cells in the TME and microRNAs (miRs) present in their cargo could play important roles in the communication between NB cells and the TME. This review article discusses these new aspects of the TME in NB and the impact that information on the TME landscape in NB will have in the design of precise, biomarker-integrated clinical trials.
Review • Journal
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
1year
Our findings demonstrate that SHMT2 expression correlates with MYCN amplification in neuroblastoma cells. SHMT2 plays an important role in neuroblastoma cellular proliferation via regulation of the PI3K/AKT2 pathway. SHMT2 does not appear to regulate MYCN transcription.
MYC (V-myc avian myelocytomatosis viral oncogene homolog) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • AKT2 (V-akt murine thymoma viral oncogene homolog 2) • SHMT1 (Serine Hydroxymethyltransferase 1)
|
MYCN amplification • MYC expression • AKT2 expression
1year
Inhibition of c-Myc (triptolide) could also be a potential strategy. GSEA is a powerful approach to identify upregulated genes and potential therapeutic targets. Dinaciclib-AZD5153 combination therapy can be effective against MYCN-non amplified and TERT-overexpressing neuroblastoma tumors.
MYC (V-myc avian myelocytomatosis viral oncogene homolog) • RB1 (RB Transcriptional Corepressor 1) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • TERT (Telomerase Reverse Transcriptase) • AURKA (Aurora kinase A) • E2F1 (E2F transcription factor 1)
|
MYCN amplification
|
dinaciclib (MK-7965) • AZD5153 • TriptoSar (triptolide)
1year
MYCN overexpression in mesenchymal neuroblastoma was sufficient to induce adrenergic identity and sensitize cells to CYC065. CYC065, used together with temozolomide, a reference therapy for relapsed neuroblastoma, caused long-term suppression of neuroblastoma growth in vivo, highlighting the clinical potential of CDK9/2 inhibition in the treatment of MYCN-amplified neuroblastoma.
Journal
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
|
temozolomide • fadraciclib (CYC065)
1year
Consequently, 7 genes, such as DAD1, PPIA, NOTCH2, PGK1, BUB1, EIF2S1, and TCF7L2, were found to be closely associated with both event-free survival (EFS) and overall survival (OS). In conclusion, the present study identified functional circRNAs and predicted their functionality in neuroblastoma cell lines, which not only improved the understanding of circRNAs in neuroblastoma, but also provided the evidences for the related researchers.
Preclinical • Journal
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • NOTCH2 (Notch 2) • RAC1 (Rac Family Small GTPase 1) • TCF7L2 (Transcription Factor 7 Like 2)
|
MYCN amplification
1year
P1, N=85, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Recruiting --> Active, not recruiting | N=36 --> 85
Enrollment closed • Enrollment change
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
|
Danyelza (naxitamab) • cyclophosphamide intravenous
1year
While the function of CD34 in NB evolution requires further in-depth investigation, careful consideration should be exercised for autologous stem cell rescue with CD34 selection in NB patients. Graphical abstract.
Journal
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • CD133 • CD34 (CD34 molecule)
|
MYCN amplification • CD34 positive
1year
This cell line showed resistance to broad spectrum chemotherapy consistent with the patient's poor response but sensitivity to the synergistic effects of panobinostat-bortezomib and carboplatin-panobinostat associations. From these cells we established a cell line derived xenograft model that closely recapitulated the tumor dissemination pattern of the patient and served to evaluate whether triple chemotherapy significantly prolonged survival of the animals. We report novel genomic alterations in two cases of metastatic MCYNamplRB1+/+ that may be associated with chemotherapy resistance and in vitro/in vivo models that serve as basis for tailoring therapy in these cases.
Clinical • Journal
|
TP53 (Tumor protein P53) • RB1 (RB Transcriptional Corepressor 1) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
TP53 mutation • MYCN amplification
|
carboplatin • bortezomib • Farydak (panobinostat)
1year
ARRY-520, an inhibitor of kinesin spindle protein (KSP), was among those causing reduced viability...Furthermore, treatment of mice harboring orthotopic neuroblastoma PDX tumors resulted in increased survival. Our results suggested that KSP inhibition could be a promising treatment strategy in children with high-risk neuroblastoma.
Preclinical • Journal
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
|
filanesib (ARRY-520)
1year
P2, N=500, Recruiting, Giselle SaulnierSholler | Trial completion date: Sep 2026 --> Sep 2032 | Trial primary completion date: Sep 2025 --> Sep 2027
Clinical • Trial completion date • Trial primary completion date
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • IL2 (Interleukin 2)
|
MYCN amplification
|
dasatinib • Nexavar (sorafenib) • Zykadia (ceritinib) • Zolinza (vorinostat) • isotretinoin oral
1year
Correlation analysis showed that all prognostic genes were negatively correlated with MYCN amplification. Cox analysis identified 5 independent prognostic genes (ARHGAP15, ABCA9, CCL19, SLAMF8, and CD1C).
Journal
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • IL7R (Interleukin 7 Receptor) • CCL19 (C-C Motif Chemokine Ligand 19) • GZMA (Granzyme A)
|
MYCN amplification
1year
SCA are not randomly distributed and are concentrated on recurrent chromosomes. The most frequently affected chromosomes identify prognostic factors in specific risk groups. SCA are associated with older age and MNA. We have identified a small subset of patients with better outcome that share whole-chromosome 19 numeric gain, suggesting its use as a prognostic biomarker in NB.
Journal
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
Chr del(11q) • MYCN amplification
1year
This year is the 30th anniversary of the identification of NCYM/MYCNOS gene. On this special occasion, we summarize the current understanding of molecular functions and the clinical significance of NCYM and discuss future directions to achieve therapeutic strategies targeting NCYM.
Clinical • Clinical data • Review • Journal
|
MYC (V-myc avian myelocytomatosis viral oncogene homolog) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
1year
Genetic propensity to taller childhood height and shorter adult height were associated with MYCN-amplified neuroblastoma risk, suggesting that biological pathways affecting growth trajectories and pubertal timing may contribute to MYCN-amplified neuroblastoma etiology.
Clinical • Journal
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
1year
P1, N=36, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Jan 2021 --> Jan 2022 | Trial primary completion date: Jan 2021 --> Jan 2022
Trial completion date • Trial primary completion date
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
|
Danyelza (naxitamab) • cyclophosphamide intravenous
1year
 There is a significant mortality observed in stage 4S/MS neuroblastoma infants with a dismal outcome observed in those patients with MYCN amplification and 1p/11q deletion. Those patients suitably amenable for conservative management or surgery to excise the primary tumor carry the best prognosis.
Review • Journal
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
Chr del(11q) • MYCN amplification
1year
P1, N=44, Recruiting, Dana-Farber Cancer Institute | Trial completion date: Oct 2022 --> Jun 2022 | Trial primary completion date: Oct 2020 --> Jun 2021
Clinical • Trial completion date • Trial primary completion date
|
MYC (V-myc avian myelocytomatosis viral oncogene homolog) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification • MYC expression
|
fimepinostat (CUDC-907)
1year
By systematically screening the compound perturbagens, the gene expression levels of MTHFD2 and PAICS were specifically suppressed by anisomycin and apicidin across cell lines, and our co-treatment results also displayed synergistic inhibition of MNA neuroblastoma cell proliferation. Collectively, targeting a combination of MYCN-targeted genes that interrupts the interconnection of metabolic pathways may overcome drug toxicity and improve the efficacy of current therapeutic agents in MNA neuroblastoma.
Journal
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • PAICS (Phosphoribosylaminoimidazole Carboxylase And Phosphoribosylaminoimidazolesuccinocarboxamide Synthase)
|
MYCN amplification
1year
Genomic aberrations of resectable non-MYCN-amplified stage 2 neuroblastomas have a distinct age-dependent prognostic impact. Chromosome 1p loss is a risk factor for relapse but not for diminished OS in patients 18months. In older patients with SCA, a randomized trial of postoperative chemotherapy compared with observation alone may be indicated.
Journal
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
1year
Plasma MYCN/NAGK ratios increased in patients with progressive disease and relapse. Thus, we conclude that determination of the plasma MYCN/NAGK ratio by qPCR is a non-invasive and reproducible method to measure MYCN amplification in patients with NB.
Clinical • Journal
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
1year
Clinical • Enrollment closed
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
|
cisplatin • carboplatin • doxorubicin hydrochloride • etoposide IV • vincristine • daunorubicin • topotecan • melphalan • Unituxin (dinutuximab) • thiotepa • Leukine (sargramostim) • cyclophosphamide intravenous • dexrazoxane • isotretinoin oral
1year
Patients presented at a later age with more advanced disease in LMICs. Management was limited by the lack of resources and genetic studies for improved NB classification. Further research is needed to develop modified diagnostic and treatment protocols for LMICs in the face of limited resources.
Journal
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
1year
 Our results indicate on a preliminary level the importance of IDRF as a prognostic tool for surgical removal of pelvic NB.
Clinical • Clinical data • Journal
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
1year
Pralatrexate demonstrated effective inhibition of cell growth and viability. The higher potency of pralatrexate compared to methotrexate, a drug with high levels of toxicity, suggests pralatrexate may be a safer alternative to methotrexate as an effective chemotherapeutic agent in the treatment of patients with high-risk neuroblastoma.
Preclinical • Journal • PARP Biomarker
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • CASP3 (Caspase 3)
|
MYCN amplification
|
methotrexate • Folotyn (pralatrexate)
1year
Functional iron deficiency at the time of initial neuroblastoma diagnosis predicted lower event-free survival. Long-term effects of iron supplementation in neuroblastoma patients with different types of iron deficiency need to be further studied.
Clinical • Journal
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
1year
Conclusions The results of treatment depended on the tumor subtype, presence of metastases, MYC amplification and MGMT methylation. In the absence of unfavorable factors, the survival was the same as in molecular subgroup4.
Clinical
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
1year
Conclusions Here we are confirming the full reliability of nanopore sequencing as a novel rapid and cheap assay for methylation-based MB subgrouping. We now plan to implement this technology to other embryonal tumors of the central nervous system.
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
1year
Conclusions This study provides novel insights into the genomic background of MYCN non-amplified NB. Activation of immune-related pathways in the high-risk group and the results of TMB and mutational signature analyses collectively suggest the need for further investigation to discover potential immunotherapeutic strategies for NB.
Tumor Mutational Burden • IO biomarker
|
TMB (Tumor Mutational Burden) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • MUC16 (Mucin 16, Cell Surface Associated)
|
TMB-H • MYCN amplification
1year
Conclusions All relapses were found in patients over 18 months, with SCA profile. Patients with unfavorable biologic and genomic profile should have radiotherapy considered and be followed for over 5 years.
Clinical
|
ALK (Anaplastic lymphoma kinase) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification • ALK mutation
1year
This finding supports the need to make multiple tests on multiple samples from tumors and recurrent tumors. Cases that was diagnosed as high risk advanced stage have less heterogeneity.
Clinical • Next-generation sequencing
|
ARID1A (AT-rich interaction domain 1A) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • GSTP1 (Glutathione S-transferase pi 1) • RECQL5 (RecQ Like Helicase 5)
|
ARID1A mutation • MYCN amplification • RECQL5 mutation
1year
Conclusions Distinct drug susceptibility predictions for neuroblastoma were identified by commercially-available molecular profiling and in-vitro drug screening. Personalized medicine strategies for neuroblastoma may benefit from combined genotype-phenotype approaches, but require further cross-validation.
TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • ARID1A (AT-rich interaction domain 1A) • JAK2 (Janus kinase 2) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • TSC2 (TSC complex subunit 2) • ARID1B (AT-Rich Interaction Domain 1B)
|
MYCN amplification • TSC2 mutation
1year
The aim of the study was evaluation of safety and efficacy of immunotherapy with dinutuximab beta (DB) and chemotherapy with irinotecan and temozolomide in patients with NBL relapse or progression. Objective response was observed in 4/6 pts (67%), including 3/6 pts (50%) with CR. It may be an option in therapy resistant patients, but it seems to have no benefit in patients who relapse during immunotherapy.
Clinical • Combination therapy
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
|
temozolomide • irinotecan • Qarziba (dinutuximab beta)
1year
Conclusions PERK-related pathway is activated in MYCN-amplified NB cells, by which promotes autophagy and eventually promotes cell survival. GSK2606414 is a specific PERK inhibitor that restrains autophagy and enhances cell death.
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
|
GSK2606414
1year
2-year EFS and OS for 1st CR patients with no prior ABMT (n=27) is 62.2%, 95% CI = (38.4%; 100%) and 80.2%, 95% CI = (55.7%; 100%). Conclusions Naxitamab-based immunotherapy is effective in consolidating first and second remission HR-NB.
Clinical
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • CSF2 (Colony stimulating factor 2)
|
MYCN amplification
|
Danyelza (naxitamab)
1year
Consolidation by HSCT, radiotherapy, and maintenance therapy improved the outcome for responders to salvage therapy. Initial front-line targeted therapy like antiGD2 is needed to improve the outcome, especially for those who are chemo resistant.
Clinical
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
1year
Shimada: 38% favourable histology NB,32% unfavourable histology NB.Five patients with PD and 3/5 died...Deaths of stage 2 and 4S patients related to PD. Treatment results were acceptable and consistent with the literature.
Clinical
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
|
Contrave (naltrexone/bupropion)
1year
85 percent of patients diagnosed with neuroblastoma by 18MS were classified as very low-risk. 18MS in Osaka does not seem to be effective in finding advanced cases of neuroblastoma.
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
1year
Conclusions BNB was more common in children during the first months of life and more likely to have distant metastases corresponding to stage 4S disease. 3-year EFS and 3-year OS was significantly higher in the group of patients with BNB in comparison to UNB.
Clinical
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
1year
Conclusions The 3-year OS of HR-NB in the single center was 53.9%, and 5-year OS was 43.1%. APBSCT can improve the prognosis of patients with bone or bone marrow metastasis and can retard recurrence or progression in patients with MYCN amplification.
Clinical
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
1year
For patients in the stage 2B group, chemotherapy should be intensified. APBSCT can effectively improve the survival rate of patients with NB, especially high-risk patients.
Clinical
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
1year
Conclusions The surrenal and paraspinal tumors in IRG-NB were approximately equal.Survival rates were similar in CCT group and HDCT+HSCT group. HRG survival rates were consistent with the literature.Progressive disease was the major cause of death.
Clinical
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
Chr del(11q) • MYCN amplification
1year
Conclusions Treosulfan-melphalan regimen was associated with low TRM and safe use in patients who had received MIBG-therapy. Additional studies are needed to assess the long-term prognosis of patients who received treosulfan.
Clinical
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
|
melphalan • Ovastat (treosulfan)
1year
P1, N=68, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Aug 2020 --> Aug 2021 | Trial primary completion date: Aug 2020 --> Aug 2021
Clinical • Trial completion date • Trial primary completion date
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
|
Danyelza (naxitamab)
1year
This study indicates that Dac effectively induces a RIG-I-related innate immune response and apoptotic signaling primarily in SK-N-AS NB cells by hypomethylating DDX58/RIG-I promoter, elevated mtROS and increased dsRNA. Dac can potentiate the cytotoxic effects of CDDP and poly(I:C) in NB cells.
Journal
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
|
cisplatin • decitabine
1year
MYCN overexpression also suppressed response to cisplatin-etoposide chemotherapy, with similar findings made upon MYCL overexpression. Pharmacological inhibition of USP7 resensitized chemoresistant MYCN-overexpressing PDX models to chemotherapy in vivo. Our findings show that MYCN overexpression drives SCLC chemoresistance and provide a therapeutic strategy to restore chemosensitivity.
Journal
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • MYCL (MYCL Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification • MYCL overexpression
|
cisplatin • etoposide IV
1year
AH liquid biopsy is a minimally invasive, in vivo alternative to tissue analysis for the simultaneous identification of RB1 variants and SCNAs in RB eyes.
Clinical • Journal
|
RB1 (RB Transcriptional Corepressor 1) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification • RB1 mutation • RB1 deletion
1year
Further, oral administration of USP7 inhibitors inhibits MM.1S (multiple myeloma; TP53 wild-type) and H526 (small cell lung cancer; TP53 mutant) tumor growth in vivo. Our work confirms that USP7 is a promising, pharmacologically tractable target for the treatment of cancer.
Preclinical • Journal
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
TP53 mutation • MYCN amplification
1year
Here, we investigated the efficacies of approved antifolates, methotrexate, pemetrexed, and raltitrexed (RTX), on MYCN-amplified and nonamplified neuroblastoma cell lines. Interestingly, RTX treatments induced single-stranded DNA damage response in MYCN-amplified cells to a greater extent than in the non-amplified cells. We propose that the high DNA replication stress and elevated levels of DNA damage, which are a result of deregulated expression of MYCN target genes, could be the cause of increased sensitivity to RTX.
Journal
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification • TYMS expression
|
pemetrexed • methotrexate • Tomudex (raltitrexed)
1year
HFRT led to 5 year-survival rate similar to other treatments combined with chemotherapy, with a reduced treatment duration of only six weeks. We confirm MSFOP 98 results, and the prognostic value of molecular status in patients with medulloblastoma, even in the absence of chemotherapy. IQ is more preserved in children with medulloblastoma who received exclusive HFRT and reduced local boost, IQ decline is delayed compared with patients receiving standard regimen. HFRT may be appropriate for patients who do not consent or are not eligible to prospective clinical trials or for patients from developing countries for whom aplasia or ileus may be difficult to manage, in a context of high cost/effectiveness constraints and for whom shortened duration of RT may be easier to implement.
Retrospective data • Journal
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
MYCN amplification
1year
However, no significant alterations were observed. Our data indicate a key role of the binding and cleavage of the AURKA transcript in an MCPIP1-dependent suppressive effect on neuroblastoma cells.
Journal
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • AURKA (Aurora kinase A)
|
MYCN amplification
1year
P, Available, Memorial Sloan Kettering Cancer Center
Clinical • New trial
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
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MYCN amplification
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Danyelza (naxitamab)
1year
Journal
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
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MYCN amplification
1year
Journal
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • BTK (Bruton Tyrosine Kinase)
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MYCN amplification
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cisplatin • ibrutinib • Calquence (acalabrutinib)
1year
This study suggests that the SRARP inactivation presents a robust biomarker in predicting molecular and clinicopathological features, and treatment response in malignancies.
Clinical • Clinical data • Journal
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TP53 (Tumor protein P53) • NF1 (Neurofibromin 1)
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TP53 mutation • NF1 mutation • MYCN amplification
1year
We found several highly significant RBPs including RPL22L1, RNASEH2A, PTRH2, MRPL11 and AFF2, which remain uncharacterised in neuroblastoma. Although not all RBPs appear suitable for drug design, or carry prognostic significance, we show that several RBPs have strong rationale for inhibition and mechanistic studies, representing an alternative, but nonetheless promising therapeutic strategy in neuroblastoma treatment.
Journal
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • AFF2 (AF4/FMR2 family member 2)
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MYCN amplification
1year
Corticosteroid therapy, broad-spectrum antibiotic therapy, and cardiovascular support with mechanical ventilation were immediately instituted, and the child recovered without sequelae. The presented case emphasizes that life-threatening complications can occur during granulocyte colony-stimulating factor administration, and patient surveillance is warranted, especially if high leukocyte counts are observed or the patient exhibits cardiopulmonary signs.
Clinical • Journal
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
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MYCN amplification
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Neupogen (filgrastim)
1year
Overexpression of dominant negative BMPR1B, treatment with a BMPR1B inhibitor and treatment with GDF5, which signals via BMPR1B, showed that BMPR1B signalling is required for optimal neuritogenesis in NB cells, suggesting that loss of BMPR1B may alter neuritogenesis. The present study shows that expression of distinct BMPRs is associated with different survival outcomes in NB.
Journal
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
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MYCN amplification
1year
Our experiments also revealed that several signaling pathways underlie the selective elimination of neuroblastoma cells by the ST013381 and ST022328 compounds. In summary, we have identified two novel compounds with a strong cytotoxic effect in vitro as promising agents for the treatment of neuroblastoma.
Journal
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
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MYCN amplification
1year
In addition to its chemosensitizing effects, CCI52 and CCI52-14 inhibited the growth of MYCN-amplified high-risk neuroblastoma cell lines and delayed tumor progression in a MYCN-driven, transgenic mouse model of neuroblastoma. These multifunctional inhibitors may be useful for the further development of anticancer agents and as tools to better understand 6-MP metabolism.
Journal
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
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MYCN amplification
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mercaptopurine delayed release (DR6MP)
1year
Given the effect of MYCN amplification on poor outcome in NB, novel treatments targeting MYCN should be developed for patients with NB.
Clinical • Journal
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
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MYCN amplification
1year
The MYC amplification corresponded with poor prognosis, the large cell/anaplastic variant of MBL, and the non-WNT/non-SHH molecular subtype.
Journal
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
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MYC amplification • MYCN amplification
over1year
Clinical • Journal
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
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MYCN amplification
over1year
These findings are presented in the context of data from three other studies describing similar cases. Therefore, a combined total of 27 MYCN amplified spinal cord ependymoma cases have now been reported in the literature, warranting their consideration as a distinctive subtype of spinal cord ependymoma (SP-EPN-MYCN) with their unique molecular characteristics and aggressive clinical behavior.
Journal
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
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MYCN amplification
over1year
OBP-301 and OBP-702 significantly suppressed the growth of subcutaneous CHP-134 tumors. Thus, these hTERT-driven oncolytic adenoviruses are promising antitumor agents for eliminating MYCN-amplified NB cells via E2F1-mediated suppression of MYCN protein.
Journal
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TP53 (Tumor protein P53) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • TERT (Telomerase Reverse Transcriptase) • E2F1 (E2F transcription factor 1)
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MYCN amplification
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pfifteloxin (OBP-702) • telomelysin (OBP-301)
over1year
In patients with stage 4 high-risk neuroblastoma who have responded to induction therapy, CME of the primary tumor is associated with improved survival and local control after HDT, local radiotherapy (21 Gy), and immunotherapy.
Clinical • Journal
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
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MYCN amplification
over1year
Furthermore, we identified 26 commonly upregulated and 311 downregulated genes in UHR-NB from all 4723 immune-related genes. While 43 KEGG pathways with molecular functions were enriched in the downregulated immune-related genes, only the P53 signaling pathway was enriched in the upregulated ones, which suggested that UHR-NB was a TP53 related subtype with reduced immune activities.
Journal
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
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MYCN amplification
over1year
Cytotoxicity studies against the human embryonic kidney cell (HEK-293) showed compounds 1, 2 and 3 were ineffective in the non-cancer cells at concentrations approximating their IC against the NB cell lines. These results may lead to safer and more effective treatment options for NB patients especially for those with high-risk NB.
Journal
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
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MYCN amplification
over1year
Lastly, using the Connectivity Map (CMap), we identified potential drugs targeting the MB stemness signature. Our findings based on stemness indices might advance the development of objective diagnostic tools for quantitating MB stemness and lead to novel biomarkers that predict the survival of patients with MB or the efficacy of strategies targeting MB stem cells.
Journal
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • GLI2 (GLI Family Zinc Finger 2)
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MYCN amplification
over1year
MYCN target genes ARMC6, DCTPP1, EIF4G1, ELOVL6, FBL, PRMT1, E2F1 and RPS19 had significant prognostic effects in pediatric neuroblastoma. And neuroblastoma patients without MYCN amplification and low EIF4G1 expression had best prognosis.
Clinical • Journal
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • E2F1 (E2F transcription factor 1)
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MYCN amplification
over1year
Our findings might facilitate improved understanding of the mechanism of pediatric NB pathogenesis. However, functional evaluation and replication of these results in other populations are still needed.
Clinical • Journal
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • NEUROG2( Neurogenin 2)
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MYCN amplification
over1year
Patients < 4 weeks old with neuroblastoma stage 4S are at risk of fatal outcome caused by progression of liver metastases. In other patients, tumor regression is characterized by a rapid biochemical normalization that precedes radiological regression.
Clinical • Journal
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
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MYCN amplification
over1year
In a panel of neuroblastoma cell lines, MYCN amplification or MYCN expression resulted in increased cell death in response to a range of PARP inhibitors (niraparib, veliparib, talazoparib and olaparib) compared to the response seen in non-expressing/amplified cells...Olaparib also sensitized MYCN expressing cells to camptothecin- and temozolomide-induced cell death to a greater degree than non-expressing cells...This effect is exaggerated by inhibition of PARP, resulting in S-phase specific DNA damage and ultimately increased tumour cell death. PARP inhibition alone or in combination with classical chemotherapeutics is therefore a potential therapeutic strategy for neuroblastoma and may be more effective in MYCN expressing tumours.
Journal • PARP Biomarker
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
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MYCN amplification
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Lynparza (olaparib) • temozolomide • Zejula (niraparib) • irinotecan • Talzenna (talazoparib) • veliparib (ABT-888)
over1year
Excellent survival was achieved with this treatment algorithm, with reduction of therapy for subsets of patients. More-effective treatment strategies still are needed for infants with unfavorable biology stage 4 disease.
Clinical • Journal
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
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MYCN amplification
over1year
Although MYCN amplification is rare in ependymomas, the current and previously reported cases suggest that this is associated with higher-grade histology, spinal location, and often unfavorable prognosis. The clinical significance and therapeutic implications of MYCN amplification in ependymomas require further evaluation.
Clinical • Journal
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
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MYCN amplification
over1year
Neuroblastomas arising in the adrenal gland are more likely to harbor structural DNA aberrations including MYCN amplification, whereas thoracic tumors show defects in mitotic checkpoints resulting in hyperdiploidy. Despite the general association of ALK mutations with high-risk disease, thoracic tumors are more likely to harbor gain-of-function ALK aberrations. Site of origin is likely reflective of stage of sympathetic nervous system development when malignant transformation occurs and is a surrogate for underlying tumor biology.
Journal
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ALK (Anaplastic lymphoma kinase) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • BARD1 (BRCA1 Associated RING Domain 1)
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MYCN amplification • ALK mutation
over1year
Finally, using RNA sequencing, we identify several potential tumor suppressor genes that are reactivated by G9a inhibition in NB, including the CLU, FLCN, AMHR2, and AKR1C1-3. Together, our study underlines the under-appreciated role of G9a in NB, especially in MYCN-amplified tumors.
Clinical • Journal
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EZH2 (Enhancer of zeste 2 polycomb repressive complex 2 subunit) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • FLCN (Folliculin)
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MYCN amplification
over1year
An excellent overall correlation between MYCN gene status by FISH and MYCN protein expression by IHC was confirmed. MYCN IHC in NB with reflexing to FISH in equivocal cases is potentially useful in a limited-resource setting. Evaluation of effectiveness using a larger cohort and optimization to perform MYCN IHC manually is needed.
Clinical • Journal
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
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MYCN amplification
over1year
P2, N=45, Suspended, National Cancer Institute (NCI) | Trial completion date: Mar 2022 --> Jun 2021 | Trial primary completion date: Mar 2022 --> Jun 2021
Clinical • Trial completion date • Trial primary completion date
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
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MYCN amplification
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cisplatin • carboplatin • doxorubicin hydrochloride • etoposide IV • vincristine • daunorubicin • topotecan • melphalan • Unituxin (dinutuximab) • thiotepa • Leukine (sargramostim) • cyclophosphamide intravenous • dexrazoxane • isotretinoin oral
over1year
This study provides a guideline for performing NGS data analysis pipeline on pool-seq and low-coverage sequencing data in conjunction. To get more conclusive outcomes of these two strategies, we recommend using cancer data having higher mutation rates and larger pools.
Journal
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RB1 (RB Transcriptional Corepressor 1) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
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MYCN amplification • RB1 mutation
over1year
Of note, the low number of CSV CTCs seems equivalent to low tumor load because the prevention therapy difluoromethylornithine yields faster reduction of relapse risk when none or only 1-2 CSV CTCs (every 6 mL) are present in the blood samples compared to >3 CSV CTCs. To the best of our knowledge, this is the first study that directly observes CTCs in under remission NB patients for relapse prediction and the first to gather sequential CSV CTC data in any study in a long-term longitudinal manner.
Clinical • Observational data • Journal • Circulating Tumor Cells
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • VIM (Vimentin)
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MYCN amplification
over1year
Myxopapillary ependymoma and subependymoma have been retained as histopathologically defined tumor types, but the classification has dropped the distinction between classic and anaplastic ependymoma. While the cIMPACT-NOW group considered that data to inform assignment of grade to molecularly defined ependymomas are insufficiently mature, it recommends assigning WHO grade 2 to myxopapillary ependymoma and allows grade 2 or grade 3 to be assigned to ependymomas not defined by molecular status.
Review • Journal
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • YAP1 (Yes associated protein 1)
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MYCN amplification
over1year
Therefore, ATRX and MYCN represent an unusual example, where inactivation of a tumor-suppressor gene and activation of an oncogene are incompatible. This synthetic lethality may eventually be exploited to improve outcomes for patients with high-risk neuroblastoma.
Journal
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • ATRX (ATRX Chromatin Remodeler)
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MYCN amplification • ATRX mutation
over1year
Reactive Oxygen Species (ROS) and glutathione (GSH) levels were detected by fluorescence and luminescence probes respectively...Pharmacologically, strategies targeting glutamine metabolism may prove beneficial in Myc-driven tumors. Consideration of MycN/c-Myc status in selecting neuroblastoma patients for glutamine metabolism treatment will be important to avoid potential radioresistance.
Journal
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MYC (V-myc avian myelocytomatosis viral oncogene homolog) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
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MYCN amplification • MYC overexpression • MYC expression
over1year
Lastly, analysis of KISS1 levels in NB patient tumors using the R2: Genomics Analysis and Visualization Platform revealed that KISS1 expression positively correlated with AHR, and high KISS1 expression predicted better survival for patients. In conclusion, our results indicate that AHR is a novel prognostic biomarker for NB, and that overexpression or activation of AHR offers a new therapeutic possibility for NB patients.
Journal
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • AHR (Aryl hydrocarbon receptor)
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MYCN amplification
over1year
Chromosome band 11q23 deletion predicts poor prognosis only in bone marrow metastatic neuroblastoma patients without MYCN amplification. Combined assessment of the two markers was much superior to single-marker assessment in recognizing the patients at a high risk of disease progression.
Clinical • Journal
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
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MYCN amplification
over1year
Decreasing the expression of MYCN in IMR32 cells via siRNA transfection inhibited cell motility by a shear stress of 0.4 Pa. These results suggest that MYCN-amplified neuroblastoma cells under high shear stress migrate to distant organs due to high cell motility, allowing cell migration to lymphatic vessels and venules.
Journal
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
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MYCN amplification
over1year
4-[F]FGln PET can provide a valuable clinical tool in the assessment of metabolic glutamine uptake in MYCN-amplified neuroblastoma. ASCT2-targeted therapy may provide a supplementary method in MYCN-amplified neuroblastoma treatment.
Journal
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • CASP3 (Caspase 3)
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MYCN amplification
over1year
Improved end-induction response in high-risk neuroblastoma is associated with longer survival. Patients with 11q LOH are less likely to respond to induction therapies and should be prioritised for novel approaches in future trials.
Clinical • Journal
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
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MYCN amplification
over1year
Our analysis resulted in a comprehensive list of prognostic chromosome bands supported by strong statistical evidence. In particular, the chr11p14 gain event provided additional prognostic value in addition to well-established clinical factors, including MYCN status, and thereby represents a novel candidate cytogenetic biomarker with high clinical potential. Additionally, this computational framework could be readily extended to other cancer types, such as leukemia.
Journal
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
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MYCN amplification
over1year
In a recent issue of Nature, Debruyne et al. demonstrate that resistant MYCN-amplified ALK-mutated neuroblastoma cells overexpress BORIS, resulting in wide-ranging changes in chromatin interaction and transcriptional reprogramming.
Journal
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
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MYCN amplification • ALK mutation • ALK amplification
over1year
The tumor suppressive properties of DHA and ELOVL2 are repressed by the MYCN and PRC1 jointly, which suggests a new epigenetic mechanism of MYCN-mediated fatty acid regulation and indicates PRC1 inhibition as a potential novel strategy to activate ELOVL2 suppressive functions.
Journal
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
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MYCN amplification
over1year
MCYN amplification and low ATM protein expression are determinants of ATRi sensitivity in NB cell lines. ATR inhibition by VE-821 is synergistic with olaparib at sub lethal concentrations (<1 µM) and further increases the replication stress caused by PARP inhibition.
Preclinical • Combination therapy • PARP Biomarker
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ATM (ATM serine/threonine kinase) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
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MYCN amplification • ATM expression
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Lynparza (olaparib) • VE-821
over1year
83/101 patients had failed prior anti-GD2 mAb (m3F8, dinutuximab, or naxitamab) therapy before vaccine: one mAb (n=62), two mAbs (n=15), or all three (n=6). Even with prior disease progressions, anti-GD2 (though not anti-GD3) seroconversion was associated with notable long-term survival among HR-NB patients previously thought to be unsalvageable. A randomized trial to assess the role of beta-glucan in seroconversion is actively accruing patients.
P2 data • Late-breaking abstract
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
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MYCN amplification
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Danyelza (naxitamab) • Unituxin (dinutuximab)
over1year
In conclusion, high c-MYC independent of genomic amplification, not MYCN amplification, is associated with disease progression in neuroblastoma. The MK2-mediated OCT4 transcriptional activation is a novel mechanism for MYC activation in PD neuroblastoma and provides a potential novel therapeutic target.
IO biomarker
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MYC (V-myc avian myelocytomatosis viral oncogene homolog) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • POU5F1 (POU Class 5 Homeobox 1)
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MYCN amplification • MYC expression
over1year
2T-T had a mean IC50 of 0.37±0.58uM(mean R2=0.9±0.07).Empty liposomes caused no cytotoxicity in any cell line. We found no difference in IC50 according to S or N type (0.50±0.65vs 0.35±0.58(p=ns)). The mean IC50 of MYCN-amplified cells was 0.47±0.63,while that of non-MYCN-amplified was 0.031±0.029(n=2), suggesting no difference in cytotoxicity based on MYCN status.
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
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MYCN amplification
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topotecan • liposomal topotecan (FF-10850)
over1year
Since this pathway is also activated during chemotherapy and promotes NB cells resistance to treatment, NPY/Y5R may also be involved in the secondary dissemination of the recurrent tumors. If the role of Y5R in NB metastasis is validated in preclinical models, this NPY receptor may become a potential therapeutic target preventing the disease dissemination.
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
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MYCN amplification
over1year
Our data show potent anti-stem cell maintenance as well as anti-proliferative, anti-migratory, anti-viability and pro-apoptotic activity of both ONC201 and ONC206 on cancer cell lines, with ONC206 showing greater potency than ONC201. Our future directions include utilizing a combinatorial multi-modality therapy to treat a panel of pediatric and adult neurological tumors with ONC 201/206 and other selective inhibitors of tumorigenic pathways to completely eliminate the highly resistant sub-population of cancer stem cells, and delay malignant recurrence.
Preclinical
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KDR (Kinase insert domain receptor) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • HSP90AA1 (Heat Shock Protein 90 Alpha Family Class A Member 1Heat Shock Protein 90 Alpha Family Class A Member 1)
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MYCN amplification
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ONC201 • ONC206
over1year
He subsequently received six months of adjuvant chemotherapy with gemcitabine plus capecitabine, derived from evidence on pancreatic adenocarcinoma due to the size of his original tumor...The patient declined further chemotherapy and his treatment was switched to Encorafenib (BRAF inhibitor) plus Binimetinib (MEK inhibitor)... While BRAF rearrangements as described in the literature may occur in 15-23% of patients with acinar cell carcinoma of the pancreas, BRAF activating mutations and in particular the BRAF V600E substitution has not been reported. This particular substitution is commonly present in melanoma, hairy cell leukemia, Langerhans cell histiocytosis and less frequently in lung and colon cancer. A combination of BRAF and MEK inhibition may be used in patients with tumors harboring this activating mutation with variable efficacy across different histologies.
BRAF (B-raf proto-oncogene) • CDKN2A (Cyclin-dependent kinase inhibitor 2A) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
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BRAF V600E • BRAF V600 • CDKN2A mutation • MYCN amplification • miR138 underexpression + miR497 overexpression
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gemcitabine • capecitabine • Braftovi (encorafenib) • Mektovi (binimetinib)
over1year
In neuroblastoma, we identified five novel methylation-dependent subgroups, which correlate with known molecular and clinical data. Six candidate SL genes were identified in methylation cluster 3, which consists almost exclusively of high-risk MYCN amplified cases.ConclusionWe have demonstrated that SL genes, specific for defined molecular subtypes of cancer, can be identified utilising a novel approach combining methylation/expression data in multiple cancer types.
ETV6 (ETS Variant Transcription Factor 6) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • FAT1 (FAT atypical cadherin 1)
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MYCN amplification
over1year
There is no single best latent dimensionality or compression algorithm for analyzing gene expression data. Instead, using features derived from different compression models across multiple latent space dimensionalities enhances biological representations.
Journal
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
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MYCN amplification
over1year
Clinical • New P2 trial • Combination therapy
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
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MYCN amplification
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temozolomide • irinotecan • Unituxin (dinutuximab) • Leukine (sargramostim) • isotretinoin oral