Cancer Research - Europa

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• 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 158 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
Coordinator Guy Storme GEIE-LINC (Groupement Européen d’Intérêt Économique – Liaison Network for Cancer) Brussels, Belgium secretariat@geie-linc.org Scientifi c Coordinator Enzo Medico The Oncogenomics Centre Institute for Cancer Research and Treatment Candiolo (TO), Italy enzo.medico@ircc.it Partners Mariano Barbacid Centro Nacional de Investigaciones Oncologicas Madrid, Spain barbacid@cnio.es Annemarie Poustka Deutsches Krebsforschungszentrum Heidelberg, Germany a.poustka@dkfz.de Rene Bernards Nederlands Kankerinstituut/Antoni van Leeuwenhoek Ziekenhuis Amsterdam, The Netherlands r.bernards@nki.nl Johannes L. Bos University Medical Center Utrecht Utrecht, The Netherlands johannes.l.bos@med.uu.nl EARLY DETECTION, DIAGNOSIS AND PROGNOSIS Marco A. Pierotti Fondazione Istituto FIRC di Oncologia Molecolare Milano, Italy marco.pierotti@istitutotumori.mi.it Rolf Apweiler European Molecular Biology Laboratory Heidelberg, Germany apweiler@ebi.ac.uk George Panayotou Biomedical Sciences Research Centre ‘Alexander Fleming’ Vari, Greece g.panayotou@fleming.gr Nancy Hynes Novartis Forschungsstiftung, Zweigniederlassung Friedrich Miescher Institute for Biomedical Research Basel, Switzerland nancy.hynes@fmi.ch Bernhard Sixt Agendia BV Slotervaart Medical Center 9D, Amsterdam, The Netherlands bernhard.sixt@agendia.com Stephan Geley University of Innsbruck Medical School Institute of Pathophysiology Innsbruck, Austria stephan.geley@uibk.ac.at Edvard Smith Karolinska Institutet Stockholm, Sweden edvard.smith@crc.ki.se Anne Ridley King’s College London, United Kingdom Carl-Henrik Heldin Ludwig Institute for Cancer Research Uppsala, Sweden c-h.heldin@licr.uu.se Claudio Schneider Consorzio Interuniversitario Biotecnologie Trieste, Italy schneider@sci.area.trieste.it Walter Birchmeier Max-Delbrück-Center for Molecular Medicine Berlin Berlin, Germany wbirch@mdc-berlin.de Yosef Yarden Weizmann Institute of Science Rehovot, Israel yosef.yarden@weizmann.ac.il Michaela Renzulli ALTA Ricerca e Sviluppo in Biotechnologie SRL Sienna, Italy renzulli@altaweb.eu Project number LSHC-CT-2004-503438 EC contribution € 6 000 000 Duration 54 months Starting date 01/06/2004 Instrument IP Project website www.transfog.org 159
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PROJECT SYNOPSES CANCER RESEARCH PR
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CANCER RESEARCH PROJECTS FUNDED UND
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TABLE OF CONTENTS FOREWORD - CANCER
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Prevention 97 EPIC 98 EUROCADET 100
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CANCER: COMBATING A COMPLEX DISEASE
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Biology Cancer is a disease ethat t
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p53 activators ASPP Partner 5 NFkap
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Keywords | Angiogenesis | vasculoge
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Keywords | Tumour-host interactions
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Keywords | Breast | metastasis | ge
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Keywords | Identifi cation of novel
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Keywords | Systems biology | modell
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Keywords | Oncology | anticancer th
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• public health research coupled
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Expected results We will construct
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Potential applications Our DNA is u
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Microscopic examination of tissue s
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Pluripotent embryonic stem cells ar
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• Decryption of the leukaemia cel
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• identifi cation of molecular ta
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A B C LT-HSC CSC The Cancer Stem Ce
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X-ray diff raction of target drug c
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using pathway-specifi c reporter ce
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Keywords | Kinases | pediatric panc
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Keywords | Lymphangiogenesis | angi
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Keywords | Breast cancer | metastas
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Keywords | Mitosis | phosphorylatio
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Keywords | Therapy | genome | telom
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Keywords | Multiple myeloma | cance
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Keywords | p53 tumour suppressor |
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Development of eff ective anti-canc
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Coordinator Patrick A. Curmi INSERM
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Drosophila as a model system for tu
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Normal cell growth and epithelial l
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effi ciently with cancer cell proli
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A high-throughput assay of transcri
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Coordinator Ewa Sikora Nencki Insti
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Expected results The SIROCCO consor
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Keywords | Epigenetics | gene regul
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Keywords | Hereditary | tricarboxyl
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Keywords | HSV-1 | hepatocellular c
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Keywords | Apoptosis | autophagy |
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Keywords | Tumour | host | signalli
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Aetiology The uncontrolled cell gro
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Coordinator Rosalind Eeles Reader i
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The parallelogram approach in CARCI
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Keywords | Melanoma | genetics | na
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Keywords | Virus | bacteria | HPV |
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Keywords | Breast | prostate | gene
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Prevention The fact that preventing
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Coordinator Elio Riboli Imperial Co
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Coordinator Jan Willem Coebergh Joh
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Coordinator Jose M a Benlloch Conse
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BAMOD Breath-Gas Analysis for Molec
Page 110 and 111: BioCare Molecular Imaging for Biolo
Page 112 and 113: These centres of excellence will in
Page 114 and 115: Expected results Optimise the benef
Page 116 and 117: 114 Cell proliferation and apoptosi
Page 118 and 119: COBRED Colon and Breast cancer Diag
Page 120 and 121: DASIM Diagnostic Applications of Sy
Page 122 and 123: Expected results Primarily, the res
Page 124 and 125: Coordinator John A. Foekens Dept. o
Page 126 and 127: 124 Aim Drop-Top has two major obje
Page 128 and 129: Coordinator Gorka Ochoa Progenika B
Page 130 and 131: Expected results The E.E.T.-Pipelin
Page 132 and 133: e developed by eTUMOUR is likely to
Page 134 and 135: Coordinator Angel Porgador Ben-Guri
Page 136 and 137: • the design of a compact assembl
Page 138 and 139: Potential applications We believe t
Page 140 and 141: Tumor initiation, progression to ma
Page 142 and 143: MolDiag-Paca Novel Molecular Diagno
Page 144 and 145: NEMO Nano based capsule-Endoscopy w
Page 146 and 147: OVCAD Ovarian Cancer - Diagnosis of
Page 148 and 149: P-MARK Validation of recently devel
Page 150 and 151: POC4life Multiparametric quantum do
Page 152 and 153: PROMET Prostate cancer molecular-or
Page 154 and 155: Micrometastasis in the bone marrow.
Page 156 and 157: and pharmaco-kinetics studies. This
Page 158 and 159: Coordinator Raffaella Giavazzi Isti
Page 163 and 164: Treatment Two major problems when t
Page 165 and 166: Coordinator Lluis M. Mir UMR 8121 C
Page 167 and 168: Potential applications ANGIOSTOP ha
Page 169 and 170: Green-fl uorescence protein- expres
Page 171 and 172: Coordinator Robert Hawkins Universi
Page 173 and 174: Expected results The BACULOGENES pr
Page 175 and 176: descriptors of the molecules to be
Page 177 and 178: Keywords | Therapeutic vaccine | im
Page 179 and 180: Keywords | Cancer chemotherapy | dr
Page 181 and 182: Keywords | Children | cancer | leuk
Page 183 and 184: Chimaeric TCR shown in context of n
Page 185 and 186: Andrea Splendiani Leaf Bioscience s
Page 187 and 188: Coordinator Anne O’Garra The Medi
Page 189 and 190: Coordinator Jacques Bartholeyns IDM
Page 191 and 192: Structure Driven Drug Design The in
Page 193 and 194: • acquire fundamental knowledge a
Page 195 and 196: Terry Jones Victoria University of
Page 197 and 198: Potential applications The use of t
Page 199 and 200: groups and management structures. T
Page 201 and 202: T. Barbui Azienda Ospedaliera-Osped
Page 203 and 204: Keywords | Mantle cell lymphoma | t
Page 205 and 206: Keywords | Hypoxia | HIF | pericell
Page 207 and 208: Keywords | Radiation-induced compli
Page 209 and 210: Keywords | Gene therapy | adenoviru
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Keywords | Dependence receptors | a
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Keywords | Photodynamic therapy | a
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Keywords | Ovarian cancer | thymidy
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Keywords | Quality assurance | clin
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Keywords | Circadian | clocks | cel
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Keywords | Anticancer therapy | onc
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Coordinator Monika Lusky Transgene
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6 000 women over a three-year perio
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Keywords | Solid tumours | apoptosi
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Keywords | Lymphoma | leukaemia | v
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Coordinator Riccardo Dolcetti Centr
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CCPRB Cancer Control using Populati
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EPCRC The European Palliative Care
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EUROCAN+PLUS Feasibility Study for
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EUSTIR A European strategy for the
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NORMOLIFE Development of new therap
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Scientifi c Model Systems The compl
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Performance of benchmarking exercis
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• markers correlating with the im
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Indices - Keywords Indices - Partne
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● disease markers 131 ● DNA dam
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● renal 77 ● replication 219
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Bos, Nico A. 56 Boskovic, Darinka 2
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Geley, Stephan 159 Georgopoulos, Li
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Lingner, Joachim 54 Linial, Michal
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Ragno, Pia 115 Rainford, Martyn 92
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Vernos, Isabelle 22 Veronesi, Umber
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● Centre Hospitalier Universitair
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● IFOM - Fondazione Istituto FIRC
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● National University of Ireland
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● University of Bari 174 ● Univ
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HOW TO OBTAIN EU PUBLICATIONS Our p
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