Cancer Research - Europa

The parallelogram approach in CARCINOGENOMICS
for developing predictive screens
Animal
in vivo
Animal cells
in vitro
• optimise cell systems into more robust cellular systems
with an extended life span, stable phenotype, and xenobiotic
metabolic competence;
• explore the suitability of embryonic stem cells as an
alternative source of robust, human-derived cells for
assessing target organ-specifi c carcinogenic actions;
• discern the biological pathways which in the predictive
models are essential for class discrimination, and to test
the pathway models for predicting carcinogenicity;
• build an in silico model for chemical carcinogenesis of
the liver;
• describe inter-individual diff erences in the response to
carcinogenic challenges;
• develop a specialized chip with high throughput features,
in order to facilitate testing of large numbers of
chemicals at high speed and low costs;
• pre-validate of the developed models according the
ECVAM guidelines;
• investigate how the novel genomics-based in vitro tests
for genotoxicity and carcinogenicity may fi t within the
EU regulatory and legal frameworks;
• establish a European public infrastructure giving an integrated
view of the genomics data but also the associated
phenotypical information;
• disseminate the outcome of the study to potential users.
Human
in vivo
Human cells
in vitro
Expected results
The project will deliver a battery of mechanism-based in vitro
tests accounting for various modes of carcinogenic action.
Based on ‘omics’ technologies, these tests will be designed
to cover major target organs for carcinogenic action e.g. the
liver, the lung, and the kidney.
Potential applications
In developing these toxicogenomics-based tests as alternatives
to current chronic animal models for evaluating
genotoxic and carcinogenic properties of chemicals, this
project will signifi cantly contribute to better hazard and risk
evaluation studies. In order to study the impact of such knowledge
including the availability of toxicogenomics-based
predictive screens on existing legislation and recent regulatory
initiatives, CARCINOGENOMICS features a separate
sub-Workpackage on associated legal and regulatory issues.
The CARCINOGENOMICS consortium involves various SMEs
in the areas of robust in vitro cellular systems, genomics
analysis and bioinformatics, as well as with regard to high
throughput technologies enabling accelerated and more
effi cient testing.
AETIOLOGY 89