Objective
Angiostatic compounds have made their way into the daily clinical management of cancer, but their impact on patient survival is rather limited. This is likely due to the fact that most current drugs are antagonists of tumor produced growth factors, a strategy expected to induce drug resistance. A better strategy would be to target the tumor vasculature directly. Several markers of tumor endothelial cells have been described but most of them lack sufficient specificity.
The applicant proposes to use Next Generation Sequencing (NGS) to identify the population of genes specifically expressed in primary prostate carcinoma and its metastases. Subsequently, this population of genes is screened for genes that are re-used during angiogenesis, and consequently overexpressed in the tumor endothelium. Prioritization of targets will be done by (i) level of (over)expression, (ii) membrane expression or secretion and (iii) existence of human ortho/homologs. After initial validation by qPCR in the source transcriptomes used for NGS, further validation of the targets will be done through loss- and gain-of-function assays. For 2-3 targets monoclonal antibodies will be generated. These antibodies will be tested in in vitro angiogenesis bioassays, and applicability will be preliminary tested in a preclinical mouse tumor model. Finally, the human ortho/homologs of the gene will be identified and validated for overexpression in human tumors.
The novelty of the proposed work is the NGS approach for selection of tumor endothelial markers, through screening for high expression in the full tumor transcriptome and absence in healthy full body RNA.
The prior experience of the applicant and the host laboratory will help the current project to succeed in reaching its goals.
In our view, it is feasible to develop a new vascular targeting strategy, ready for translation to clinical testing. The proposed work will strongly reinforce the collaboration between two European institutes.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- medical and health sciences basic medicine pharmacology and pharmacy drug resistance
- medical and health sciences clinical medicine oncology
- natural sciences biological sciences genetics RNA
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP7-PEOPLE-2013-IEF
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Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Coordinator
1081 HV Amsterdam
Netherlands
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.