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TECNEC SIGNED

Preclinical concept validation of tumor endothelial cell metabolism for novel anti-angiogenic therapy

Total Cost €

EC-Contrib. €

Partnership

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TECNEC project word cloud

Explore the words cloud of the TECNEC project. It provides you a very rough idea of what is the project "TECNEC" about.

differ endothelial platform data manner mice tumors main methodology background network lack nec clinical validated tecs isolated pioneered though conditional vessel knockout sufficient hyperactive shrna omics house vitro perform rationale inhibiting biomex healthy hypothesize silico nothing inhibition negative gems angiogenic fuelling genome dismissed blood tumor tissue vivo deregulated metabolism patients transcriptomic modeling validate therapy cancer necs validation bioinformatics novelty computational versus driving fundamentally normalize block followed inhibitors preclinical hyper biologically horizons efficacy normal promise cells predict treatments screen pioneering treatment metabolic nourish models promises angiogenesis demonstrated genes rank stimulate anti metabolomic construct analyze tec activate

Project "TECNEC" data sheet

The following table provides information about the project.

Coordinator	VIB VZW Organization address address: RIJVISSCHESTRAAT 120 city: ZWIJNAARDE - GENT postcode: 9052 website: www.vib.be contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.
Coordinator Country	Belgium [BE]
Total cost	2˙500˙000 €
EC max contribution	2˙500˙000 € (100%)
Programme	1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
Code Call	ERC-2016-ADG
Funding Scheme	ERC-ADG
Starting year	2017
Duration (year-month-day)	from 2017-11-01 to 2022-10-31

Partnership

Take a look of project's partnership.

#	participants	country	role	EC contrib. [€]
1	VIB VZW VIB VZW Organization address address: RIJVISSCHESTRAAT 120 city: ZWIJNAARDE - GENT postcode: 9052 website: www.vib.be contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.	BE (ZWIJNAARDE - GENT)	coordinator	2˙500˙000.00

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Project objective

MAIN GOAL: To characterize the metabolic changes, fuelling growth of tumor endothelial cells (TECs) versus normal healthy endothelial cells (NECs), and identify & validate metabolic genes, deregulated in TECs, as targets for anti-angiogenic cancer therapy.

BACKGROUND & RATIONALE: Tumors stimulate blood vessel growth (angiogenesis) to nourish cancer cells, but current anti-angiogenic treatments lack sufficient efficacy. NECs are widely used for anti-angiogenesis development, but TECs, the real target cells, have been dismissed, even though they differ fundamentally from NECs. We pioneered NEC metabolism research and demonstrated that inhibition of specific metabolic pathways can block angiogenesis. Nothing is however known on TEC metabolism. I hypothesize that TECs “hyper-activate” their metabolism in a tissue-specific manner, and that targeting TEC metabolism is a novel concept for inhibiting tumor angiogenesis.

METHODOLOGY: We will perform a transcriptomic and metabolomic analysis of TECs & NECs isolated from cancer patients, use an in-house developed bioinformatics platform (BIOMEX) to analyze the omics data in order to rank deregulated metabolic genes, and construct TEC-tailored genome scale metabolic network models (GEMs) allowing in silico computational modeling to predict metabolic targets that affect TEC but not NEC growth. The in vitro angiogenic activity of top targets will be biologically validated directly or after a negative selection shRNA-based screen, followed by validation in preclinical tumor models in vivo, using conditional knockout mice. All procedures are operational. Deliverables include in vivo validated metabolic targets, driving tumor angiogenesis.

NOVELTY, OVERALL & CLINICAL IMPACT: These pioneering studies on TEC metabolism promise to open up new horizons/opportunities for cancer research. Treatment with inhibitors of the validated targets promises to normalize hyperactive TEC metabolism as a novel anti-angiogenic cancer therapy.

Publications

List of publications.
year	authors and title	journal	last update
2018	Shawez Khan, Federico Taverna, Katerina Rohlenova, Lucas Treps, Vincent Geldhof, Laura deÂ Rooij, Liliana Sokol, Andreas Pircher, Lena-Christin Conradi, Joanna Kalucka, Luc Schoonjans, Guy Eelen, Mieke Dewerchin, Tobias Karakach, Xuri Li, Jermaine Goveia, Peter Carmeliet EndoDB: a database of endothelial cell transcriptomics data published pages: D736-D744, ISSN: 0305-1048, DOI: 10.1093/nar/gky997	Nucleic Acids Research 47/D1	2019-09-02

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