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Content archived on 2024-05-29

Epigenetic treatment of neoplastic disease

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.

Fields of science (EuroSciVoc)

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Topic(s)

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Call for proposal

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FP6-2004-LIFESCIHEALTH-5
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Funding Scheme

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NoE - Network of Excellence

Coordinator

CENTRE EUROPÉEN DE RECHERCHE EN BIOLOGIE ET MÉDECINE - GROUPEMENT D'INTÉRÊT ECONOMIQUE
EU contribution
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Total cost

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Participants (13)

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