TRIPLE-BC

Identification and functional validation of drugable targets/pathways for triple negative breast cancer

Coordinatore	ERASMUS UNIVERSITAIR MEDISCH CENTRUM ROTTERDAM    more Spiacenti, non ci sono informazioni su questo coordinatore. Contattare Fabio per maggiori infomrazioni, grazie.
Nazionalità Coordinatore	Netherlands [NL]
Totale costo	2˙495˙101 €
EC contributo	2˙495˙101 €
Programma	FP7-IDEAS-ERC Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
Code Call	ERC-2012-ADG_20120314
Funding Scheme	ERC-AG
Anno di inizio	2013
Periodo (anno-mese-giorno)	2013-04-01   -   2018-03-31

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	UNIVERSITEIT LEIDEN  Organization address address: RAPENBURG 70 city: LEIDEN postcode: 2300 RA contact info Titolo: Mr. Nome: Ton Cognome: Brouwer Email: send email Telefono: 31715273149 Fax: 31715275269	NL (LEIDEN)	beneficiary	569˙044.15
2	STICHTING HET NEDERLANDS KANKER INSTITUUT  Organization address address: PLESMANLAAN 121 city: AMSTERDAM postcode: 1066 CX contact info Titolo: Dr. Nome: Henri Cognome: Van Luenen Email: send email Telefono: 31205122097 Fax: +31 20 669 1383	NL (AMSTERDAM)	beneficiary	96˙384.00
3	ERASMUS UNIVERSITAIR MEDISCH CENTRUM ROTTERDAM  Organization address address: 's Gravendijkwal 230 city: ROTTERDAM postcode: 3015CE contact info Titolo: Mr. Nome: Bart Cognome: Van Der Hoorn Email: send email Telefono: +31 10 7030137 Fax: +31 10 7034803	NL (ROTTERDAM)	hostInstitution	1˙829˙673.41
4	ERASMUS UNIVERSITAIR MEDISCH CENTRUM ROTTERDAM  Organization address address: 's Gravendijkwal 230 city: ROTTERDAM postcode: 3015CE contact info Titolo: Prof. Nome: Johannes Albert Cognome: Foekens Email: send email Telefono: +31 10 7044369 Fax: +31 10 7044370	NL (ROTTERDAM)	hostInstitution	1˙829˙673.41

Mappa

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 Obiettivo del progetto (Objective)

'Patients suffering from triple-negative breast cancer (TNBC) have a poor prognosis as these tumors frequently confer resistance against chemotherapeutic agents and lack drug targets such as estrogen receptor, progesterone receptor, and epidermal growth factor receptor 2. Insufficient knowledge on the biology of this specific breast tumor type and its heterogeneity hinder the identification of potential novel drug targets. Lethality enhancer screening is an ideal approach to identify new drug targets in tumors with specific genetic aberrations. We plan to adapt this concept of synthetic lethality by anticipating that while TNBC cells confer resistance to available anticancer drugs, specific knock down of particular genes by RNA-interference (RNAi) may result in a synergistic cell killing. Another important aspect of our approach is that we will concentrate in our screens on the top 500 candidate genes shown to be crucial in TNBC for cellular processes. The genes will be prioritized by Bayesian network analysis on prior knowledge on clinical TNBC from our own extensive genomics and proteomics studies, the literature, next generation sequencing efforts, and databases listing drugability of targets. We will employ RNAi-based knock down of drugable targets in 22 cell lines to reveal genes essential for drug resistance in TNBC. In addition to 2D cultures, screens will also be applied to 3D cultures, which are thought to better reflect the in vivo situation. The most effective combinations for each TNBC subtype will further be functionally investigated in vitro and in vivo to unravel the molecular nature of the synthetic lethality. Finally, translational studies will be performed to establish the potential clinical relevance of the identified targets/pathways in large numbers of human TNBC and non-TNBC tumors on tissue microarrays. It is expected that the newly designed (combination) therapies result in a decline in TNBC mortality and reduction of healthcare costs.'