ABC

Targeting Multidrug Resistant Cancer

Coordinatore	RESEARCH CENTRE FOR NATURAL SCIENCES, HUNGARIAN ACADEMY OF SCIENCES    more Spiacenti, non ci sono informazioni su questo coordinatore. Contattare Fabio per maggiori infomrazioni, grazie.
Nazionalità Coordinatore	Hungary [HU]
Totale costo	1˙499˙640 €
EC contributo	1˙499˙640 €
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-2010-StG_20091118
Funding Scheme	ERC-SG
Anno di inizio	2012
Periodo (anno-mese-giorno)	2012-01-01   -   2016-12-31

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	RESEARCH CENTRE FOR NATURAL SCIENCES, HUNGARIAN ACADEMY OF SCIENCES  Organization address address: PUSZTASZERI UTCA 59-67 city: BUDAPEST postcode: 1025 contact info Nome: Aniko Cognome: Kiraly Email: send email Telefono: +36 1 279 3100	HU (BUDAPEST)	hostInstitution	1˙499˙640.00
2	RESEARCH CENTRE FOR NATURAL SCIENCES, HUNGARIAN ACADEMY OF SCIENCES  Organization address address: PUSZTASZERI UTCA 59-67 city: BUDAPEST postcode: 1025 contact info Titolo: Dr. Nome: Gergely Cognome: Szakacs Email: send email Telefono: +36 1 372 4321 Fax: +36 1 3724300	HU (BUDAPEST)	hostInstitution	1˙499˙640.00

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 Obiettivo del progetto (Objective)

'Despite considerable advances in drug discovery, resistance to anticancer chemotherapy confounds the effective treatment of patients. Cancer cells can acquire broad cross-resistance to mechanistically and structurally unrelated drugs. P-glycoprotein (Pgp) actively extrudes many types of drugs from cancer cells, thereby conferring resistance to those agents. The central tenet of my work is that Pgp, a universally accepted biomarker of drug resistance, should in addition be considered as a molecular target of multidrug-resistant (MDR) cancer cells. Successful targeting of MDR cells would reduce the tumor burden and would also enable the elimination of ABC transporter-overexpressing cancer stem cells that are responsible for the replenishment of tumors. The proposed project is based on the following observations:

- First, by using a pharmacogenomic approach, I have revealed the hidden vulnerability of MDRcells (Szakács et al. 2004, Cancer Cell 6, 129-37);

- Second, I have identified a series of MDR-selective compounds with increased toxicity toPgp-expressing cells (Turk et al.,Cancer Res, 2009. 69(21));

- Third, I have shown that MDR-selective compounds can be used to prevent theemergence of MDR (Ludwig, Szakács et al. 2006, Cancer Res 66, 4808-15);

- Fourth, we have generated initial pharmacophore models for cytotoxicity and MDR-selectivity (Hall et al. 2009, J Med Chem 52, 3191-3204).

I propose a comprehensive series of studies that will address thefollowing critical questions:

- First, what is the scope of MDR-selective compounds?

- Second, what is their mechanism of action?

- Third, what is the optimal therapeutic modality?

Extensive biological, pharmacological and bioinformatic analyses will be utilized to address four major specific aims. These aims address basic questions concerning the physiology of MDR ABC transporters in determining the mechanism of action of MDR-selective compounds, setting the stage for a fresh therapeutic approach that may eventually translate into improved patient care.'