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Genomic screening of the Embryo for Novel targets in the tumor Endothelium (GENE)
Start date: May 1, 2013, End date: Apr 30, 2015 PROJECT  FINISHED 

"Several angiogenesis inhibitors are in the market for treatment of cancer, but efficiency in terms of prolongation of survival is still very moderate. This can be explained by induction of resistance to therapy, since most agents neutralize tumor produced growth factors.An alternative and preferred strategy would be to directly target the tumor endothelial cells, which will not easily mutate to resist treatment due to genetic stability. It is hypothesized that by mining the pool of genes that have embryo-specific functions, new and fully specific markers of tumor endothelial cells can be found.The approach will be to isolate the full transcriptome of mouse embryos at early and late developmental stages, and compare it with adult mouse isolates. The pool of purely embryo-specific genes will be screened for expression in the transcriptome of FACS sorted tumor endothelial cells. Genomic screening will be performed, by next-generation sequencing, to maximize the identification of specific genes or splice variants. Gene function will be tested by genetic loss- and gain-of-function approaches in in vitro angiogenesis assays. Transmembrane and secreted tumor endothelial specific molecules will receive priority. Endogenous binding partners will be identified by yeast 2-hybrid technology and peptide design will yield specific drugs. Also, antibodies against target molecules will be generated. Initial preclinical testing will be part of this project. Translation of the technology for treatment of patients, i.e. finding the human orthologs, and extensive preclinical testing will be beyond the scope of this project and will be subject of a new grant application."
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