Neuroblastoma
|
0.700 |
Biomarker
|
disease |
BEFREE |
In this issue of Science Signaling, Umapathy et al. identify the kinase extracellular signal-regulated kinase 5 (ERK5) as a central mediator that enables ALK to boost MYCN expression, and they show that inhibiting ERK5 in concert with ALK reduced neuroblastoma cell viability in vitro and in xenograft tumor models.
|
25351246 |
2014 |
Neuroblastoma
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Altogether, this study provides novel insights into ALK mutation dynamics in a neuroblastoma model harbouring two ALK mutations.
|
31452835 |
2019 |
Neuroblastoma
|
0.700 |
AlteredExpression
|
disease |
BEFREE |
CHD9, a cancer driver gene, was the most significantly altered (4.0% of cases) after ALK.Other genes (PTK2, NAV3, NAV1, FZD1 and ATRX), expressed in neuroblastoma and involved in cell invasion and migration were mutated at frequency ranged from 4% to 2%.Focal adhesion and regulation of actin cytoskeleton pathways, were frequently disrupted (14.1% of cases) thus suggesting potential novel therapeutic strategies to prevent disease progression.Notably BARD1, CHEK2 and AXIN2 were enriched in rare, potentially pathogenic, germline variants.In summary, whole exome and deep targeted sequencing identified novel cancer genes of clinically aggressive neuroblastoma.
|
27009842 |
2016 |
Neuroblastoma
|
0.700 |
Biomarker
|
disease |
BEFREE |
Our study provides strong rationale for clinical trial of ALK-positive neuroblastoma using ibrutinib or the combination of ibrutinib and ALK inhibitors.
|
30013190 |
2018 |
Neuroblastoma
|
0.700 |
Biomarker
|
disease |
BEFREE |
We review the basic aspects of MYCN, Trk, and ALK in both neural development and in neuroblastoma.
|
30848386 |
2019 |
Neuroblastoma
|
0.700 |
Biomarker
|
disease |
BEFREE |
In particular, for the latter, given the frequency of ALK gene deregulation in neuroblastoma patients, we discuss on second-generation ALK inhibitors in preclinical or clinical phases developed for the treatment of neuroblastoma patients resistant to crizotinib.We summarise how Omics drive clinical trials for neuroblastoma treatment and how much the research of biological targets is useful for personalised medicine.
|
28178969 |
2017 |
Neuroblastoma
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
This small-molecule inhibitor was shown to efficiently inhibit the growth of patient-derived and established neuroblastoma xenograft models expressing mutated ALK.
|
26747894 |
2016 |
Neuroblastoma
|
0.700 |
AlteredExpression
|
disease |
BEFREE |
ALK is also found expressed in neural crest-derived tumors such as human neuroblastomas or glioblastomas but its role is not fully elucidated.
|
17611412 |
2007 |
Neuroblastoma
|
0.700 |
PosttranslationalModification
|
disease |
BEFREE |
Expression of the ALK tyrosine kinase gene in neuroblastoma.
|
10793082 |
2000 |
Neuroblastoma
|
0.700 |
Biomarker
|
disease |
BEFREE |
The observed unexpected upregulation of ADM warrants further investigation in relation to putative ALK resistance in neuroblastoma patients currently undergoing ALK inhibitor treatment.
|
29290991 |
2017 |
Neuroblastoma
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Furthermore, our data represent the first demonstration of ALK-wt transforming capacity, as ALK-wt expression in JoMa1 cells, likewise ALK-F1174L, or ALK-R1275Q, in absence of exogenous Myc-ERT activity, was sufficient to induce the formation of aggressive and undifferentiated neural crest cell-derived tumors, but not to drive NB development.
|
24947326 |
2014 |
Neuroblastoma
|
0.700 |
Biomarker
|
disease |
BEFREE |
The second-generation ALK inhibitor alectinib effectively induces apoptosis in human neuroblastoma cells and inhibits tumor growth in a TH-MYCN transgenic neuroblastoma mouse model.
|
28455243 |
2017 |
Neuroblastoma
|
0.700 |
AlteredExpression
|
disease |
BEFREE |
Here, we show that both wild-type and gain-of-function mutants in ALK are able to stimulate transcription at the MYCN promoter and initiate mRNA transcription of the MYCN gene in both neuronal and neuroblastoma cell lines.
|
22286764 |
2012 |
Neuroblastoma
|
0.700 |
Biomarker
|
disease |
BEFREE |
Developing approaches to neuroblastoma include those that target the catecholamine transporter, ubiquitin E3 ligase, the ganglioside GD2, the retinoic acid receptor, the protein kinases ALK and Aurora, and protein arginine N-methyltransferases.
|
28800395 |
2017 |
Neuroblastoma
|
0.700 |
AlteredExpression
|
disease |
BEFREE |
IHC confirmed the diagnosis by detecting the expression of ALK protein.After ALK positivity was proven, the effectiveness and safety of the crizotinib therapy was examined in 4 patients (1 alveolar rhabdomyosarcoma (RMA), 1 embryonal rhabdomyosarcoma (RME), 1 inflammatory myofibroblastic tumor (IMT), 1 NBL).
|
29081033 |
2019 |
Neuroblastoma
|
0.700 |
Biomarker
|
disease |
BEFREE |
Mechanisms of acquired resistance to ALK inhibition therapy in neuroblastoma have not yet been elucidated.
|
31614113 |
2019 |
Neuroblastoma
|
0.700 |
Biomarker
|
disease |
BEFREE |
These data support the concept of ALK-targeted immunotherapy as a highly promising therapeutic strategy for neuroblastomas with mutated or wild-type ALK.
|
22266870 |
2012 |
Neuroblastoma
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Surprisingly, thoracic neuroblastomas were more likely to harbor ALK driver mutations than adrenal cases among all cases (odds ratio = 1.89, 95% confidence interval = 1.04 to 3.43), and among cases without MYCN amplification (odds ratio = 2.86, 95% confidence interval = 1.48 to 5.49).
|
30793172 |
2019 |
Neuroblastoma
|
0.700 |
Biomarker
|
disease |
BEFREE |
Relative to free ALK-siRNA, anti-GD₂-targeted liposomal formulations of ALK-siRNA had low plasma clearance, increased siRNA stability, and improved binding, uptake, silencing and induction of cell death, and specificity for NB cells.In NB xenografts, intravenous (i.v.) injection of the targeted ALK-siRNA liposomes showed gene-specific antitumor activity with no side effects.
|
21487394 |
2011 |
Neuroblastoma
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Here we show that germline mutations in the anaplastic lymphoma kinase (ALK) gene explain most hereditary neuroblastomas, and that activating mutations can also be somatically acquired.
|
18724359 |
2008 |
Neuroblastoma
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Expression of MYCN or ALK(F1174L), one of the oncogenic ALK variants identified in primary neuroblastomas, enabled these cells to grow independently of c-MycER(T) activity in vitro and caused formation of neuroblastoma-like tumors in vivo in contrast to parental JoMa1 cells and JoMa1 cells-expressing TrkA or GFP.
|
22484425 |
2013 |
Neuroblastoma
|
0.700 |
Biomarker
|
disease |
BEFREE |
The Anaplastic Lymphoma Kinase (<i>ALK</i>) gene is frequently altered in NB, through copy number alterations and activating mutations, and represents a predisposition in NB-genesis when mutated.
|
31058082 |
2019 |
Neuroblastoma
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Alterations in anaplastic lymphoma kinase (<i>ALK</i>) gene are involved in neuroblastoma, lung cancer, and other malignancies, but its role in SCCP has not been documented.
|
29559559 |
2018 |
Neuroblastoma
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Activating mutations within the full-length ALK kinase domain, most commonly R1275Q and F1174L, which play a major role in neuroblastoma, were recently identified.
|
20632993 |
2010 |
Neuroblastoma
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
As well as MYCN amplification, activating point mutations of ALK and NRAS are associated with high-risk and relapsing neuroblastoma.
|
28602975 |
2017 |