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bioMARkers and molecular tumor classification for non-genotoxic CARcinogenesis

Obiettivo

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.

Invito a presentare proposte

IMI-JU-01-2008
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Coordinatore

NOVARTIS PHARMA AG
Contributo UE
Nessun dato
Indirizzo
LICHTSTRASSE 35
4056 Basel
Svizzera

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Regione
Schweiz/Suisse/Svizzera Nordwestschweiz Basel-Stadt
Tipo di attività
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Contatto amministrativo
Ursula Knauf (Ms)
Ricercatore principale
Jonathan Guy MOGGS (Dr)
Collegamenti
Costo totale
Nessun dato

Partecipanti (11)