Abstract

We will utilize four cell lines, two MYCN not-amplified and two MYCN amplified cell line that can be grown in a xenograft model. Among other assays we will use the Real-Time Cell Electronic Sensing System (RT-CES system;Acea Biosciences, CA, USA). The most promising targets and the appropriate siRNA will be further evaluated in the two xenograft animal models as outlined above. All positive hits will be further screened in a wider panel of NB Xenografts which will be part of a panel of the Pediatric Preclinical Testing Program (PPTP) which is currently being utilized as a pipeline to screen new drugs and make recommendation for human pediatric phase 1/2 trials (http://ctep.cancer.gov/resources/child.html. We have successfully optimized the high through put siRNA screening using a set of approximately 400 apoptosis related genes and the findings are being prepared for publication.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIABC010806-04
Application #
8157472
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2010
Total Cost
$121,144
Indirect Cost

  Institution

Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

McKinnon, Timothy; Venier, Rosemarie; Yohe, Marielle et al. (2018) Functional screening of FGFR4-driven tumorigenesis identifies PI3K/mTOR inhibition as a therapeutic strategy in rhabdomyosarcoma. Oncogene 37:2630-2644
Veschi, Veronica; Liu, Zhihui; Voss, Ty C et al. (2017) Epigenetic siRNA and Chemical Screens Identify SETD8 Inhibition as a Therapeutic Strategy for p53 Activation in High-Risk Neuroblastoma. Cancer Cell 31:50-63
Zhang, Shile; Wei, Jun S; Li, Samuel Q et al. (2016) MYCN controls an alternative RNA splicing program in high-risk metastatic neuroblastoma. Cancer Lett 371:214-24
Patel, Paresma R; Sun, Hongmao; Li, Samuel Q et al. (2013) Identification of potent Yes1 kinase inhibitors using a library screening approach. Bioorg Med Chem Lett 23:4398-403
Li, Samuel Q; Cheuk, Adam T; Shern, Jack F et al. (2013) Targeting wild-type and mutationally activated FGFR4 in rhabdomyosarcoma with the inhibitor ponatinib (AP24534). PLoS One 8:e76551
Wei, Jun S; Johansson, Peter; Chen, Li et al. (2013) Massively parallel sequencing reveals an accumulation of de novo mutations and an activating mutation of LPAR1 in a patient with metastatic neuroblastoma. PLoS One 8:e77731
Yeung, C L; Ngo, V N; Grohar, P J et al. (2013) Loss-of-function screen in rhabdomyosarcoma identifies CRKL-YES as a critical signal for tumor growth. Oncogene :
Tsang, Patricia S; Cheuk, Adam T; Chen, Qing-Rong et al. (2012) Synthetic lethal screen identifies NF-ýýB as a target for combination therapy with topotecan for patients with neuroblastoma. BMC Cancer 12:101
Chen, Qing-Rong; Yu, Li-Rong; Tsang, Patricia et al. (2011) Systematic proteome analysis identifies transcription factor YY1 as a direct target of miR-34a. J Proteome Res 10:479-87
Guo, Xiang; Chen, Qing-Rong; Song, Young K et al. (2011) Exon array analysis reveals neuroblastoma tumors have distinct alternative splicing patterns according to stage and MYCN amplification status. BMC Med Genomics 4:35