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bioMARkers and molecular tumor classification for non-genotoxic CARcinogenesis

Objective

MARCAR aims to establish reliable early markers and molecular classification of tumors in non genotoxic carcinogenesis, applying a mechanism-based approach. Benefits are improved drug safety, more efficient drug development, and progress with 3 R issues. MARCAR focuses on rodent liver, the major target organ of non-genotoxic carcinogens (NGC). However, this approach will facilitate predictions for other organs. Innovative industry-relevant experimental models will be developed: (i) Transgenic mice nulled or
humanized for NGC-responsive nuclear receptors, (ii) transgenic mice excreting marker proteins in urine, including oxidative stress reporter mice to monitor ROS production, (iii) transgenic mice allowing in vivo bioirnaging of preneoplastic lesions (PNL) and tumors, and (iv) primary cultures of human/rodent hepatocytes and their co-cultivation with mesenchymal cells which modulate carcinogenesis by NGC. In these systems, novel molecular technologies will be used for profiling the
genome, epigenome, transcriptome and proteome/phosphoproteome to provide global molecular
signatures of NGC-induced signalling. These complementary technologies in conjunction with
standardized data management and advanced marker identification algorithms will lead to molecular classification of tumors and PNL, and identify predictive molecular signatures of spontaneous vs drug induced tumors. Biomarker panels indicating the mechanisms of GC action will be derived and translated into assay systems. The validity, predictivity and robustness of biornarkers will be tested in collaboration with EFPIA, employing well—characterized pre—climcal models. For clinical translation humanized/human systems and materials from clinical trials will be tested for NGC effects on homologues of rodent biomarkers. The provision of high-quality deliverables is facilitated by complementary expertise in carcinogenesis/bioanalysis, in conjunction with know-how and in kind
contributions of EFPIA partners.

Field of science

  • /natural sciences/biological sciences/biochemistry/biomolecules/proteins
  • /natural sciences/biological sciences/genetics and heredity/genome
  • /medical and health sciences/basic medicine/pharmacology and pharmacy/drug safety

Call for proposal

IMI-JU-01-2008
See other projects for this call

Funding Scheme

JTI-CP-IMI - Joint Technology Initiatives - Collaborative Project (IMI)

Coordinator

NOVARTIS PHARMA AG
Address
Lichtstrasse 35
4056 Basel
Switzerland
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Principal investigator
Jonathan Guy MOGGS (Dr)
Administrative Contact
Ursula Knauf (Ms)

Participants (11)

UNIVERSITY OF DUNDEE
United Kingdom
EU contribution
€ 1 365 522
Address
Nethergate
DD1 4HN Dundee
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Zoe Kidd (Mrs)
CXR Biosciences Limited
United Kingdom
EU contribution
€ 1 082 648
Address
James Lindsay Place
DD1 5JJ Dundee
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Peter Mulderry (Dr)
MEDIZINISCHE UNIVERSITAET WIEN
Austria
EU contribution
€ 668 554
Address
Spitalgasse 23
1090 Wien
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Christoph Zielinski (Univ.-Prof. Dr.)
THE UNIVERSITY OF EDINBURGH
United Kingdom
EU contribution
€ 692 473
Address
Old College, South Bridge
EH8 9YL Edinburgh
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Valerie Renton (Mrs)
EBERHARD KARLS UNIVERSITAET TUEBINGEN
Germany
EU contribution
€ 1 129 064
Address
Geschwister-scholl-platz
72074 Tuebingen
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Michael Schwarz (Professor)
NATURWISSENSCHAFTLICHES UND MEDIZINISCHES INSTITUT AN DER UNIVERSITAET TUEBINGEN
Germany
EU contribution
€ 455 600
Address
Markwiesenstrasse 55
72770 Reutlingen
Activity type
Research Organisations
Administrative Contact
Günter Beck (Dipl.-Kfm)
INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
France
EU contribution
€ 655 717
Address
Rue De Tolbiac 101
75654 Paris
Activity type
Research Organisations
Administrative Contact
Ghislaine GIBELLO (-)
BOEHRINGER INGELHEIM INTERNATIONALGMBH
Germany
Address
Binger Strasse
55218 Ingelheim
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Marcus Koska (Dr.)
Bayer Pharma AG
Germany
Address
Muellerstrasse 178
13353 Berlin
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Delia Noelte (-)
UCB PHARMA SA
Belgium
Address
Allee De La Recherche 60
1070 Bruxelles
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Simon DRESSE (Mr.)
H. LUNDBECK AS
Denmark
Address
Ottiliavej 7-9
2500 Valby
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Nina Ostenfeldt (Dr.)