Cancer Research - Europa

• Development of tools for diagnostic validation of molecular
signatures for cancers of high population impact,
namely of the colon, breast and lung. This will enable
translation into clinical use of signatures obtained
through the cancer-oriented genomic screenings performed
by the participating units. In particular, the
project is expected to defi ne and validate prognostic
signatures associated with the tendency of the abovementioned
cancers to give rise to metastasis.
• Establishment of a shared bioinformatic platform for
functional oncogenomics data handling and standardisation.
This will require a concerted eff ort towards
codifi cation of the various biological assays according to
specifi c functional features analysed by each assay,
using for example the Gene Ontology as a template
(www.geneontology.org), and the sharing of analysis software
and tools. Towards the same aim, a web-accessible
platform based on the Distributed Annotation System
(www.biodas.org) will be implemented.
Expected results
The project will go through three main phases:
Phase I (year 1): Initial set-up of experimental procedures for
systematic cancer gene functional analysis and clinical validation;
establishment of standards and tools for HTP data
sharing and mining.
Phase II (years 2-3): Scaled-up, high-throughput gene functional
analysis and clinical diagnostic validation of new
cancer molecular signatures, and identifi cation of new
molecular targets for innovative cancer therapy.
Phase III (year 4): Final collection of results, dissemination of
technologies and deliverables to the European cancer
research community and cancer hospitals. Exploitation of
the achieved results, mainly as new cancer diagnosis tools
and the screening of new targets for cancer drug discovery.
The TRANSFOG project will deliver a consistent and integrated
amount of functional data on genes of, as yet,
unknown activity and biological role. In the process of reaching
this objective, the participating units will be enabled to
set up truly post-genomic eff orts toward systematic gene
functional characterisation. New technologies will be developed
that will allow exploration of gene regulatory networks,
protein- protein interactions and high-throughput cell-based
evaluation of basic biological functions, such as motility,
growth, apoptosis, invasion, adhesion, polarisation and more
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complex processes, as in vitro epithelial morphogenesis and
angiogenesis. The technologies for systematic gene functional
characterisation developed here will be useful for
functional studies involving a variety of physiological and
pathological processes, and will be made available to the
scientifi c community in the frame of a collaborative research
network. The bioinformatic networking endowed with the
project will enable participating units to share tools for data
handling, database exploration and functional gene annotation.
It will also facilitate integration of the present network
with other EC-funded networks and with the European and
global post-genomic community.
Potential applications
A crucial issue in genomics is to develop enabling technologies.
TRANSFOG will tackle this issue by developing:
• tools and standards for genomic data sharing, which will
allow the results of cancer-oriented genomic screenings
carried out by the consortium to be merged or made
available in databases, thus generating a prioritised list
of candidate cancer genes;
• plasmid collections carrying FL-cDNAs or siRNAs to achieve
gainor loss-of-functions of the identifi ed candidates.
Within a few years, competitive research will rely on the
availability of genome-wide collections enabling systematic
gene gain- or lossof- function and protein-protein interaction
studies. Similarly, only high-throughput biochemical
and biological assays will take full advantage of such collections,
together with bioinformatic resources to handle and
mine the data. A great advantage of a smaller collection
focused on cancer gene discovery, like the one proposed
here, is that it will enable functional analysis at a midthroughput
level, with a higher probability of success in the
timeframe of the project. The know-how developed in the
process of generating and employing such a collection will
provide the basis for competitive, larger-scale studies to be
carried out later on at the European level.
The willingness to understand and cure cancer will be the
driving force for generating functional genomic technologies
specifi cally aimed at improving management of the
oncological patient. Indeed, a more precise evaluation of the
tendency of a tumour to give rise to metastases will have
a great social impact, particularly in helping reduce mortality
and, at the same time, reducing overtreatment of patients
that would not require aggressive anticancer therapy, and
promoting direct, early exploration of alternative therapeutic
strategies in patients with diagnostic signatures that predict
poor prognosis.
CANCER RESEARCH PROJECTS FUNDED UNDER THE SIXTH FRAMEWORK PROGRAMME