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Epigenetic treatment of neoplastic disease

Project information

Grant agreement ID: 518417

  • Start date

    1 November 2005

  • End date

    30 April 2011

Funded under:

FP6-LIFESCIHEALTH

  • Overall budget:

    € 13 704 690

  • EU contribution

    € 10 904 474

Coordinated by:

CENTRE EUROPÉEN DE RECHERCHE EN BIOLOGIE ET MÉDECINE - GROUPEMENT D'INTÉRÊT ECONOMIQUE

France

Objective

Chromatin is epigenetically modified to regulate gene expression. Upstream signals induce complex patterns of enzyme-catalyzed modifications of DNA and histones, key protein components of chromatin. These epigenetic modifications create docking sites for other regulators and form a code that specifies transient or permanent (and heritable) patterns of genome function. In addition, epigenetic enzymes modify the activity of major transcription factors. Emerging evidence causally links altered epigenetic functions to oncogenesis, suggesting that chromatin regulators and upstream pathways are critical targets for developing novel anti-cancer drugs (epi-drugs). The demonstration that the in vivo anti-cancer activity of histone deacetylase inhibitors (HDACi's) is causally linked to induction of cancer cell-selective apoptosis has provided proof-of-principle for the potency of epi-drugs. This Consortium (EPITRON) will define and validate the concept of "epigenetic cancer treatment" from the mechanism to animal models accurately reproducing human leukemia, and extend this concept to solid tumors, in animal models of breast cancer. We will follow a multidisciplinary and integrated approach, i) define the mechanism of the anti-leukemic action of existing epi-drugs and the role of individual epi-enzymes, ii) molecularly define the tumor selectivity of HDACi-induced TRAIL death ligand, iii) validate TRAIL action in mouse models and establish "reporter mice" to monitor the in vivo activity of epi-drugs iv) generate novel epi-drugs and nuclear receptor ligands, iv) search by genome-wide epigenetic technologies novel epi-targets with emphasis on leukemia and leukemogenic oncoproteins, v) analyse the potential of epi-drug sensitization and crosstalk, and vi) analyse the response mechanism of epi-drugs in breast/colon cancer. This work will uncover the basis of cancer-selective apoptosis and provide novel types of validated tumor-selective weapons.

Coordinator

CENTRE EUROPÉEN DE RECHERCHE EN BIOLOGIE ET MÉDECINE - GROUPEMENT D'INTÉRÊT ECONOMIQUE

Address

1 Rue Laurent Fries
10142 Illkirch

France

Participants (13)

ISTITUTO EUROPEO DI ONCOLOGIA SRL

France

STICHTING KATHOLIEKE UNIVERSITEIT, MORE PARTICULARLY THE FACULTY OF SCIENCE, MATHEMATICS AND COMPUTING SCIENCE

Netherlands

UNIVERSIDADE DE VIGO

Spain

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE

France

THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE

United Kingdom

UNIVERSITY OF TURKU

Finland

EPIGENOMICS AG

Germany

CONGENIA S.R.L.

Italy

BAYER SCHERING PHARMA AG GROUP

Germany

ABCAM LIMITED

United Kingdom

DIAGENODE SA

Belgium

SECONDA UNIVERSITÀ DEGLI STUDI DI NAPOLI

Italy

UNIVERSITÀ DEGLI STUDI DI MILANO

Italy

Project information

Grant agreement ID: 518417

  • Start date

    1 November 2005

  • End date

    30 April 2011

Funded under:

FP6-LIFESCIHEALTH

  • Overall budget:

    € 13 704 690

  • EU contribution

    € 10 904 474

Coordinated by:

CENTRE EUROPÉEN DE RECHERCHE EN BIOLOGIE ET MÉDECINE - GROUPEMENT D'INTÉRÊT ECONOMIQUE

France