Cancer Research - Europa

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Coordinator Gorka Ochoa Progenika Biopharma, S.A. Parque Tecnológico de Bizkaia Edificio 801 B, Derio-Vizcaya 48160, Spain gochoa@progenika.com Partners Francois Radvanyi Institut Curie-CNRS 26 Rue d’Ulm, 75248 Cedex 05 Paris, France Francois.radvanyi@curie.fr Nuria Malats Institut Municipal d’Investigacio Medica Universitat Pompeu-Fabra Doctor Aiguader 80, Barcelona, Spain nmalats@imim.es Gordana Cerovic Genewave Bat 404-XTEC, École Polytechnique Palaiseau Cedex, France gordana.cerovic@polytechnique.fr 126 Melanie Hilanio University of Geneva B 24 rue General-Dufour Geneva, Switzerland melanie.hilario@cui.unige.ch Zivko Popov University Cyril and Methodius-Faculty of Medicine Department of Urology Vodnjanska 17 Skopje, Former Yugoslav Republic of Macedonia zivkopopov2000@yahoo.com Hader Kless NuAce Tecnologies, Ltd. 14 Moskovitz St. Rehovot, Israel hadar@nuace-bio.com Jörg Hoheisel Deutsches Krebsforschungszentrum Im Neuenheimer Feld 280 Heidelberg, Germany j.hoheisel@dkfz.de Project number LSHB-CT-2006-037739 EC contribution € 1 834 331 Duration 36 months Starting date 01/01/2007 Instrument STREP Project website www.drop-top.net CANCER RESEARCH PROJECTS FUNDED UNDER THE SIXTH FRAMEWORK PROGRAMME
Keywords | Neuroblastoma | medulloblastoma | retinoblastoma | nephroblastoma | rhabdoid | Ewing | translational research | E.E.T.-Pipeline European Embryonal Tumour Pipeline Summary Treatment of embryonal tumours (ET) is a challenge for the pediatric oncologist. Innovative translational research is required to exploit available genomic data and implement state-of-the-art technologies to overcome the defi cits of current diagnostic and treatment strategies. We will set up a Consortium of leading European institutions and SMEs with extensive clinical and technological expertise in order to establish a unique pipeline for the comprehensive development and validation of novel diagnostic tools in addition to effi cient preclinical drug development for ET. Our holistic approach includes: • validation of a chip-based diagnostic platform tailored specifi cally for ET, including analysis of genes previously shown by the Consortium to be aff ected in ET; • validation of a chip-based diagnostic platform tailored specifi cally for ET, including analysis of genes previously shown by the Consortium to be aff ected in ET; • extension of an existing database designed to warehouse complete clinical and experimental data for neuroblastoma to include all ET entities; • implementation of a virtual ‘ET-Biobank’ to improve sharing of patient samples; • functional characterisation of the most promising molecular targets previously identifi ed by the partners as a foundation for entry into a drug development pipeline; • integration of existing disease-specifi c mouse models to evaluate new treatment modalities in vivo; • initial evaluation of a screening method and antibody aff ecting ET cell invasion; • application of novel bioinformatic solutions for meta- analysis; • dissemination of the novel tools to researchers and clinical study centres in Europe. Our coordinated eff ort can achieve the critical mass to facilitate the necessary integration of research capacities for translating ET genome data into signifi cant medical progress. Involvement of clinical study centres will ensure a direct link to the bedside, aimed at improving child health and quality of life. EARLY DETECTION, DIAGNOSIS AND PROGNOSIS Problem Second to accidents, cancer is still the leading cause of death for children in Europe. Approximately 30 % of childhood malignancies are embryonal tumours (ET), often demonstrating resistance to conventional treatment approaches and being associated with lower survival rates compared to other childhood cancers. Thus, novel diagnostic and therapeutic options are urgently needed in particular for this group of tumours in order to improve survival rates and quality of life of pediatric cancer patients. The limitations of current treatment approaches include, in particular, a lack of validated postgenomic technology available for routine diagnostics and a large gap between target identifi cation in basic research eff orts and resulting pre-clinical development of novel drugs. Beyond defi ning characteristic gene expression signatures, only a limited number of studies have addressed the functional analysis of identifi ed target genes. The genetic low complexity of ET tumours provides a suitable system to identify druggable targets. Conclusive diagnosis using histology alone is diffi cult due to the uniform morphologies of the diff erent ET entities, identifying ET as an important area to complement current strategies with modern post-genomic approaches. Our approach is of particular importance for ET, as the ET entities are orphan diseases, meaning each entity does not have a large enough market to justify the costs of drug development by a private company. The identifi cation of potential targets for all ET entities should be more economically attractive for private companies. Common molecular pathways such as myc- and RB-signalling and chromosomal deletions including 1p36 and 11q loss have been previously identifi ed in diff erent ET entities by the Consortium members and others, supporting a rationale integrating all ET types. Aim The multimodal genomic and proteomic approaches proposed here provide a promising alternative for more successful tumour diagnosis, subclassifi cation and drug development for ET. This STREP will provide a coordinated strategy for the translation of basic research results into the pre-clinical arena, focusing on the implementation of stateof-the-art diagnostic tools, improvement of access to clinical material, and the effi cient combination of post-genomic research approaches with pre-clinical drug development. 127
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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
Page 77 and 78: Keywords | Epigenetics | gene regul
Page 79 and 80: Keywords | Hereditary | tricarboxyl
Page 81 and 82: Keywords | HSV-1 | hepatocellular c
Page 83 and 84: Keywords | Apoptosis | autophagy |
Page 85 and 86: Keywords | Tumour | host | signalli
Page 87 and 88: Aetiology The uncontrolled cell gro
Page 89 and 90: Coordinator Rosalind Eeles Reader i
Page 91 and 92: The parallelogram approach in CARCI
Page 93 and 94: Keywords | Melanoma | genetics | na
Page 95 and 96: Keywords | Virus | bacteria | HPV |
Page 97 and 98: Keywords | Breast | prostate | gene
Page 99 and 100: Prevention The fact that preventing
Page 101 and 102: Coordinator Elio Riboli Imperial Co
Page 103 and 104: Coordinator Jan Willem Coebergh Joh
Page 105: Coordinator Jose M a Benlloch Conse
Page 108 and 109: 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 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 160 and 161: • Development of tools for diagno
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
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Keywords | Cancer chemotherapy | dr
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Keywords | Children | cancer | leuk
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Chimaeric TCR shown in context of n
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Andrea Splendiani Leaf Bioscience s
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Coordinator Anne O’Garra The Medi
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Coordinator Jacques Bartholeyns IDM
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Structure Driven Drug Design The in
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• acquire fundamental knowledge a
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Terry Jones Victoria University of
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Potential applications The use of t
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groups and management structures. T
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T. Barbui Azienda Ospedaliera-Osped
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Keywords | Mantle cell lymphoma | t
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Keywords | Hypoxia | HIF | pericell
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Keywords | Radiation-induced compli
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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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