CORDIS
EU research results

CORDIS

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bioMARkers and molecular tumor classification for non-genotoxic CARcinogenesis

Project information

Grant agreement ID: 115001

Status

Closed project

  • Start date

    1 January 2010

  • End date

    30 June 2015

Funded under:

FP7-JTI

  • Overall budget:

    € 13 110 690

  • EU contribution

    € 6 049 578

Coordinated by:

NOVARTIS PHARMA AG

Switzerland

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.
Leaflet | Map data © OpenStreetMap contributors, Credit: EC-GISCO, © EuroGeographics for the administrative boundaries

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

CXR Biosciences Limited

United Kingdom

EU Contribution

€ 1 082 648

MEDIZINISCHE UNIVERSITAET WIEN

Austria

EU Contribution

€ 668 554

THE UNIVERSITY OF EDINBURGH

United Kingdom

EU Contribution

€ 692 473

EBERHARD KARLS UNIVERSITAET TUEBINGEN

Germany

EU Contribution

€ 1 129 064

NATURWISSENSCHAFTLICHES UND MEDIZINISCHES INSTITUT AN DER UNIVERSITAET TUEBINGEN

Germany

EU Contribution

€ 455 600

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE

France

EU Contribution

€ 655 717

BOEHRINGER INGELHEIM INTERNATIONALGMBH

Germany

Bayer Pharma AG

Germany

UCB PHARMA SA

Belgium

H. LUNDBECK AS

Denmark

Project information

Grant agreement ID: 115001

Status

Closed project

  • Start date

    1 January 2010

  • End date

    30 June 2015

Funded under:

FP7-JTI

  • Overall budget:

    € 13 110 690

  • EU contribution

    € 6 049 578

Coordinated by:

NOVARTIS PHARMA AG

Switzerland