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Expected results<br />
• The results of this project will begin to explain the molecular<br />
basis for organ-specifi c metastasis in breast cancer.<br />
• This project will identify regulatory pathways and cellular<br />
events that coordinate organ-specifi c metastasis of<br />
breast cancers. Novel targets for therapy will thereby be<br />
identifi ed.<br />
• This project will identify gene expression signatures in<br />
tumours associated with metastasis to particular organs.<br />
This will be an important advance in understanding the<br />
underlying genetic changes that regulate organ-specifi c<br />
metastasis in breast cancer.<br />
• This project will bring together European experts working<br />
on diff erent aspects of the molecular basis of tumour<br />
metastasis. As a result of coordinated eff orts, pathways<br />
that regulate metastasis to specifi c organs will be determined,<br />
and genes that play a functional role in organ-specifi c<br />
metastasis will be identifi ed.<br />
• This project will generate improved animal models for<br />
the further study of breast cancer metastasis to specifi c<br />
organs.<br />
• This project will identify gene expression signatures in<br />
primary breast tumours that predict patterns of metastasis.<br />
The application of these fi ndings will assist clinical<br />
decision making and prognostic evaluation.<br />
Potential applications<br />
The gene expression signatures in primary tumours identifi<br />
ed in this project that predict organ-specifi c metastasis<br />
and the prognosis of DCIS will have obvious potential for<br />
clinical application in diagnosis and prognostic assessment.<br />
Gene expression signatures in primary tumours associated<br />
with either organ-specifi c metastasis or progression of DCIS<br />
will be extensively validated retrospectively and as a prelude<br />
to introducing these gene expression signatures into clinical<br />
diagnosis and prognostic evaluation, we will perform prospective<br />
studies to demonstrate the effi cacy of examining<br />
gene expression signatures in primary breast cancers for<br />
predicting the likelihood and location of metastases and the<br />
probability that DCIS will progress and metastasise after<br />
partial mastectomy. The prototype microarray chips we create<br />
based on gene expression profi les produced as part of<br />
this project will be applied in the clinical setting to investigate<br />
their diagnostic and prognostic value for breast cancer<br />
in a prospective study. This will constitute a major step<br />
towards exploitation of the results. It is also highly likely that<br />
genes are identifi ed in this project will be candidate targets<br />
for the development of novel cancer therapies. The development<br />
of such therapies lies outside the time-frame and<br />
scope of the proposal.<br />
18<br />
Coordinator<br />
Jonathan Sleeman<br />
University of Heidelberg<br />
Medical Faculty Mannheim<br />
Centre for Biomedicine and Medical<br />
Technology Mannheim (CBTM)<br />
Mannheim, Germany<br />
sleeman@medma.uni-heidelberg.de<br />
Partners<br />
Frans Van Roy<br />
Dept. for Molecular Biomedical <strong>Research</strong><br />
VIB – Gent University<br />
Gent, Belgium<br />
Frans.Vanroy@dmbr.UGent.be<br />
Gerhard Christofori<br />
Institute of Biochemistry and Genetics<br />
Dept. of Clinical-Biological Sciences<br />
University of Basel<br />
Basel, Switzerland<br />
gerhard.christofori@unibas.ch<br />
Eugene Lukanidin<br />
Danish <strong>Cancer</strong> Society<br />
Institute of <strong>Cancer</strong> Biology<br />
Copenhagen, Denmark<br />
el@cancer.dk<br />
Jean-Paul Thiéry<br />
CNRS – UMR 144<br />
Institut Curie<br />
Cell Biology Department<br />
Paris, France<br />
jpthiery@imcb.a-star.edu.sg<br />
Bernd Hentsch<br />
TopoTarget Germany AG<br />
Frankfurt am Main, Germany<br />
BHe@TopoTarget.com<br />
Agnès Noël<br />
Laboratoire de Biologie des Tumeurs<br />
et du Développement<br />
Liège, Belgium<br />
agnes.noel@ulg.ac.be<br />
John Collard<br />
The Netherlands <strong>Cancer</strong> Institute<br />
Division of Cell Biology<br />
Amsterdam, The Netherlands<br />
j.collard@nki.nl<br />
Project number<br />
LSHC-CT-2004-503224<br />
EC contribution<br />
€ 3 430 273<br />
Duration<br />
42 months<br />
Starting date<br />
01/07/2004<br />
Instrument<br />
STREP<br />
Project website<br />
http://igtmv1.fzk.de/<br />
www/brecosm/<br />
Peter ten Dijke<br />
The Netherlands <strong>Cancer</strong> Institute<br />
Division of Cellular Biochemistry<br />
Amsterdam, The Netherlands<br />
& Leiden University Medical Center (LUMC)<br />
Leiden, The Netherlands<br />
p.ten_dijke@lumc.nl<br />
Roland Stauber<br />
Chemotherapeutisches Forschungsinstitut<br />
Frankfurt am Main, Germany<br />
& Johannes Gutenberg Universität Mainz<br />
Mainz, Germany<br />
rstauber@uni-mainz.de<br />
Massimo Zollo<br />
TIGEM-Telethon<br />
Naples, Italy<br />
& CEINGE Biotecnologie Avanzate, S.c.a.r.l.<br />
Naples, Italy<br />
zollo@ceinge.unina.it<br />
Peter Schlag<br />
Charité Universitätsklinikum Berlin<br />
Berlin, Germany<br />
pmschlag@charite.de<br />
CANCER RESEARCH PROJECTS FUNDED UNDER THE SIXTH FRAMEWORK PROGRAMME
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