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Content archived on 2024-06-18

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.

Call for proposal

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

Coordinator

NOVARTIS PHARMA AG
EU contribution
No data
Address
LICHTSTRASSE 35
4056 Basel
Switzerland

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Region
Schweiz/Suisse/Svizzera Nordwestschweiz Basel-Stadt
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Ursula Knauf (Ms)
Principal investigator
Jonathan Guy MOGGS (Dr)
Links
Total cost
No data

Participants (11)