Growing evidence suggests a major role for Src-homology-2-domain-containing phosphatase 2 (SHP2/PTPN11) in MYCN-driven high-risk neuroblastoma, although biologic confirmation and a plausible mechanism for this contribution are lacking.
Busulfan and melphalan versus carboplatin, etoposide, and melphalan as high-dose chemotherapy for high-risk neuroblastoma (HR-NBL1/SIOPEN): an international, randomised, multi-arm, open-label, phase 3 trial.
These data suggest integrin α<sub>v</sub>β<sub>3</sub>, MYCN/BRD4 and PTEN/PI3K/AKT signaling as biomarkers and hence therapeutic targets in neuroblastoma and support testing of the RGD integrin α<sub>v</sub>β<sub>3</sub>-targeted PI-3K/BRD4 inhibitor, SF1126 as a therapeutic strategy in this specific subgroup of high risk neuroblastoma.
These data suggest integrin α<sub>v</sub>β<sub>3</sub>, MYCN/BRD4 and PTEN/PI3K/AKT signaling as biomarkers and hence therapeutic targets in neuroblastoma and support testing of the RGD integrin α<sub>v</sub>β<sub>3</sub>-targeted PI-3K/BRD4 inhibitor, SF1126 as a therapeutic strategy in this specific subgroup of high risk neuroblastoma.
MiR-497 targets multiple genes related to the DDR, cell cycle, survival and angiogenesis, which renders this molecule a promising candidate for NB therapy.
ABCC1 and ABCC4 are thus potential targets for therapeutic suppression in high-risk neuroblastoma, and recently developed small-molecule inhibitors may be an effective strategy in treating aggressive forms of this cancer, as well as other cancers that express high levels of these transporters.
Treatment of NB cell lines with NSC-87877 results in increased p53 phosphorylation (Ser37 and Ser46) and activation, increased activation of downstream p38 effector proteins (heat shock protein 27 (HSP27) and MAP kinase-activated protein kinase 2 (MAPKAPK2)) and poly ADP ribose polymerase/caspase-3 cleavage.
From January 2004 to December 2008, 50 consecutive patients with high-risk neuroblastoma were assigned to receive tandem HDCT (high-dose chemotherapy)/auto-SCT after nine cycles of induction chemotherapy.
In addition, PK11195 significantly decreased mRNA expression of the chemotherapy resistance efflux pumps ABCA3, ABCB1 and ABCC1 in two post-relapse NB cell lines.
Thus, PEA15 and its partners ERK and RSK2 are potential targets for the development of new therapeutics to impede progression of minimal residual disease in patients with high-risk neuroblastoma.
Although autologous tandem hematopoietic SCT has improved the prognosis of patients with advanced high-risk neuroblastoma, the results remain unsatisfactory.
These results provide insights into a key epigenetic pathway responsible for modulating TERT-driven NB progression, which could represent a target for therapeutic intervention.
This is the first study to demonstrate that XN alters the expression of DR5 as well as the synergistic effect of XN on TRAIL in NB and provides a strong rationale for further preclinical analysis.
We showed that ARID1A directly caused suppression of TERT and was reliant on DNA binding and co-occupancy of the TERT promoter by the SIN3 transcription regulator family member A (SIN3A) repressor complex allowing NB differentiation to proceed.
We showed that ARID1A directly caused suppression of TERT and was reliant on DNA binding and co-occupancy of the TERT promoter by the SIN3 transcription regulator family member A (SIN3A) repressor complex allowing NB differentiation to proceed.
We showed that ARID1A directly caused suppression of TERT and was reliant on DNA binding and co-occupancy of the TERT promoter by the SIN3 transcription regulator family member A (SIN3A) repressor complex allowing NB differentiation to proceed.
Our findings demonstrated for the first time that Rad51 is a prognostic marker in NB and down-regulation of Rad51 can lead to chemo-sensitizing effect in human NB cells.
This is the first study to demonstrate that XN alters the expression of DR5 as well as the synergistic effect of XN on TRAIL in NB and provides a strong rationale for further preclinical analysis.
<b>Purpose:</b> In 2010, a Children's Oncology Group (COG) phase III randomized trial for patients with high-risk neuroblastoma (ANBL0032) demonstrated improved event-free survival (EFS) and overall survival (OS) following treatment with an immunotherapy regimen of dinutuximab, GM-CSF, IL2, and isotretinoin compared with treatment with isotretinoin alone.