Cancer Research - Europa

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ESBIC-D European Systems Biology Initiative combating complex diseases Summary It is the goal of this coordination action (CA) to establish a European framework for a systems biology approach to combat complex diseases using cancer as a prototypical problem. The coordination action will be fundamentally based on existing resources of leading research groups in Europe. It unites groups with a strong clinical focus, with experience in high throughput functional genomics as well as with computational and systems biology resources. Moreover, it brings together groups from some of the largest European cancer research organisations and centres. Problem Keywords | Systems biology | computational biology | cancer research | modelling | signalling pathways | bioinformatics and patient information | Primary targets of the Sixth Framework programme are activities for the combat of multigenic complex diseases such as cancer, diabetes, obesity, heart diseases and diseases of the nervous system. In particular, cancer is, after decades of research, still a devastating disease, responsible for roughly one quarter of the death in Europe. Essentially, the three main causes for cancer are infection, environmental infl uence and genetic predisposition. However, on a more analytical and molecular level the ontogeny of cancer is less evident and both clinical as well as basic research suggests that cancer is the result of an accumulation of many factors that promote tumour growth and metastasis. Consequently, it is not clear, if much of current cancer research, typically focussed on analysing subprocesses involving at most a few genes or gene products at a time, will ever be able to ‘understand’ such a complex phenomenon, and to form the basis for dramatic improvements in cancer treatment. It is also clear, that the current research approaches, in spite of all successes in some areas, have not resulted in any dramatic increase in the rates of cure for most common cancers. With this CA we expect to improve this situation by addressing the problem with a systems biology approach. In particular, the strong interaction of clinical and experimental data with theoretical computer modelling will be applied in an interdisciplinary and international approach. This goal will be achieved via a series of steps: • designing the protocols needed for rapid data and information exchange for the diff erent levels of cellular information; • connecting leading European research groups in a consortium that contributes existing data and computational resources and links clinical and experimental groups with computational groups; • providing standards and protocols to combine the data resources with theoretical models; • providing documentation and a series of workshops to achieve the largest possible benefi t for European cancer research. These interaction points between the diff erent expertises build the basis for measurable and verifi able targets of the project that will have a high impact on future planning and design of systems biology approaches for all complex genetic diseases. Aim Exchange and dissemination of information – combining leading EU wide resources. A particular goal of this CA will be the agglomeration and integration of relevant information from all three components. Existing resources of the partners/partner institutions will be incorporated and an immediate added-value is achieved on the European level by the correlation and integration of those components. Performance of joined studies and analyses – bridging experiment and model. There is a fundamental discrepancy in current cancer research. Much of the analysis carried out up to now has been focussed on the eff ect of single genes, resulting in models that are far too simple to explain the complex biological processes acting in cancer development. Thus, modelling at the state of the art is in most cases not very helpful for e.g. prediction of the response of patients to diff erent types of treatment or the development of new drugs. On the other hand there is the tendency to generate more and more data in an uncoordinated and non-standardized fashion. This not only increases costs but also leads to heterogeneous and often confl icting results for the relevant biological processes. Thus, experimental data generation at the state of the art is not very helpful to guide the development of theoretical models. With this CA we aim at identifying critical parameters in the course of such model development and the identifi cation of experimental protocols and strategies to measure these critical parameters in coordinated experiments that target diff erent levels of cellular information. 244 CANCER RESEARCH PROJECTS FUNDED UNDER THE SIXTH FRAMEWORK PROGRAMME
Performance of benchmarking exercises – defi ning test cases for systems biology approaches in cancer. There are many promises for health care: models of regulatory networks are necessary to understand their alterations in case of a disease and to develop methods to cure the disease. Furthermore, since there is an observable trend in health care towards an individualized and predictive medicine there will be an increasing need for the exact formulation of cellular networks and the prediction of systems behaviour in the areas of drug development, drug validation, diagnostics, and therapy monitoring. In this project we will defi ne several test cases that will show for example the performance of models for signalling pathways in the light of the experimental data resources. Organisation and management – setting up an expert group for a European wide systems approach towards the combat of cancer. So far, on the European level, there are some excellent groups and networks that focused their work in particular fi elds of genomics, proteomics, clinical research and bioinformatics. While on the one hand theses areas will need additional strengthening to remain competitive on an international level, we are still lacking an initiative that brings together these groups to fi nd common and effi cient ways to integrate and to utilise the data produced. This will be a fi rst necessary step to create a European platform for systems biology of complex diseases/cancer. Consequently a coherent structure for data acquisition and data integration for modelling has to be built. For this purpose we need to: • defi ne cancer related clinical, genomic and proteomic data sets in the context of systems biology; • improve ways of data acquisition, storage and communication procedures; • set standards for quality data integration; • defi ne common targets of systems biology modelling in cancer. Expected results A coordinated action for the systems biology of cancer will create an expandable network of partners that develop effi - cient tools for data collection, integration and modelling. In the future, this will improve our understanding and in particular our prognostic and therapeutic abilities for the complex genetic disease cancer. Potential applications Not applicable. SCIENTIFIC MODEL SYSTEMS Coordinator Hans Lehrach Max Planck Institute for Molecular Genetics Dept. Vertebrate Genomics Berlin, Germany lehrach@molgen.mpg.de Partners Annemarie Poustka German Cancer Research Centre (DKFZ) Dept. Molecular Genome Analysis Heidelberg, Germany a.poustka@dkfz.de Jean-Philippe Vert Association pour la recherche et le développement des méthodes et processus industriels Paris, France Jean-Philippe.Vert@mines.org Ron Shamir Tel Aviv University School of Computer Science Tel Aviv, Israel shamir@math.tau.ac.il Project number LSHG-CT-2005-518192 EC contribution € 350 000 Duration 24 months Starting date 01/11/2005 Instrument CA Project website http://pybios.molgen. mpg.de/ESBIC-D Crispin Miller University Manchester Paterson Institute for Cancer Research Christie Hospital NHS Trust Manchester, United Kingdom cmiller@picr.man.ac.uk Emmanuel Barillot Institut Curie Paris, France Emmanuel.Barillot@curie.fr Kurt Zatloukal Medical University of Graz Dept. of Pathology Graz, Austria Kurt.zatloukal@meduni-graz.at 245
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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
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BioCare Molecular Imaging for Biolo
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These centres of excellence will in
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Expected results Optimise the benef
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114 Cell proliferation and apoptosi
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COBRED Colon and Breast cancer Diag
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DASIM Diagnostic Applications of Sy
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Expected results Primarily, the res
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Coordinator John A. Foekens Dept. o
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124 Aim Drop-Top has two major obje
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Coordinator Gorka Ochoa Progenika B
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Expected results The E.E.T.-Pipelin
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e developed by eTUMOUR is likely to
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Coordinator Angel Porgador Ben-Guri
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• the design of a compact assembl
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Potential applications We believe t
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Tumor initiation, progression to ma
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MolDiag-Paca Novel Molecular Diagno
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NEMO Nano based capsule-Endoscopy w
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OVCAD Ovarian Cancer - Diagnosis of
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P-MARK Validation of recently devel
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POC4life Multiparametric quantum do
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PROMET Prostate cancer molecular-or
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Micrometastasis in the bone marrow.
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and pharmaco-kinetics studies. This
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Coordinator Raffaella Giavazzi Isti
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• Development of tools for diagno
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Treatment Two major problems when t
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Coordinator Lluis M. Mir UMR 8121 C
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Potential applications ANGIOSTOP ha
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Green-fl uorescence protein- expres
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Coordinator Robert Hawkins Universi
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Expected results The BACULOGENES pr
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descriptors of the molecules to be
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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
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
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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
Page 211 and 212: Keywords | Dependence receptors | a
Page 213 and 214: Keywords | Photodynamic therapy | a
Page 215 and 216: Keywords | Ovarian cancer | thymidy
Page 217 and 218: Keywords | Quality assurance | clin
Page 219 and 220: Keywords | Circadian | clocks | cel
Page 221 and 222: Keywords | Anticancer therapy | onc
Page 223 and 224: Coordinator Monika Lusky Transgene
Page 225 and 226: 6 000 women over a three-year perio
Page 227 and 228: Keywords | Solid tumours | apoptosi
Page 229 and 230: Keywords | Lymphoma | leukaemia | v
Page 231: Coordinator Riccardo Dolcetti Centr
Page 234 and 235: CCPRB Cancer Control using Populati
Page 236 and 237: EPCRC The European Palliative Care
Page 238 and 239: EUROCAN+PLUS Feasibility Study for
Page 240 and 241: EUSTIR A European strategy for the
Page 242 and 243: NORMOLIFE Development of new therap
Page 245: Scientifi c Model Systems The compl
Page 249 and 250: • markers correlating with the im
Page 251 and 252: Indices - Keywords Indices - Partne
Page 253 and 254: ● disease markers 131 ● DNA dam
Page 255 and 256: ● renal 77 ● replication 219
Page 257 and 258: Bos, Nico A. 56 Boskovic, Darinka 2
Page 259 and 260: Geley, Stephan 159 Georgopoulos, Li
Page 261 and 262: Lingner, Joachim 54 Linial, Michal
Page 263 and 264: Ragno, Pia 115 Rainford, Martyn 92
Page 265 and 266: Vernos, Isabelle 22 Veronesi, Umber
Page 267 and 268: ● Centre Hospitalier Universitair
Page 269 and 270: ● IFOM - Fondazione Istituto FIRC
Page 271 and 272: ● National University of Ireland
Page 273 and 274: ● University of Bari 174 ● Univ
Page 275 and 276: HOW TO OBTAIN EU PUBLICATIONS Our p
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