Cancer Research - Europa

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76 Coordinator Axel Imhof Adolf-Butenandt-Institut LMU Munich, Germany aimhof@med.uni-muenchen.de Project Management Julia Hochstatter Adolf-Butenandt-Institut LMU Munich, Germany Julia.Hochstatter@med.uni-muenchen.de Partners Scott Cuthill Chroma Therapeutics Oxford, United Kingdom Dirk Schuebeler Friedrich-Miescher-Institut Basel, Switzerland Manel Esteller CNIO Madrid, Spain Tony Kouzarides Gurdon Institute Cambridge, United Kingdom Project number LSHG-CT-2006-037415 EC contribution € 2 500 000 Duration 48 months Starting date 01/12/2006 Instrument STREP Project website www.smarterchromatin.eu CANCER RESEARCH PROJECTS FUNDED UNDER THE SIXTH FRAMEWORK PROGRAMME
Keywords | Hereditary | tricarboxylic acid cycle | fumarase | succinate dehydrogenase | renal | paraganglioma | leiomyoma | TCAC in <strong>Cancer</strong> Defects in the Tricarboxylic Acid (Krebs) Cycle Summary For this project, top European cancer research groups working on the association between defects in the tricarboxylic acid cycle (TCAC) and cancer form a consortium to profoundly characterise the human phenotypes to enable identifi cation and effi cient cancer prevention, and to unravel the underlying molecular mechanisms. Recent breakthrough fi ndings by the consortium participants and others have shown that defects in at least four TCAC genes – fumarate hydratase (FH, fumarase), and succinate dehydrogenase (SDH) B, C, and D – can confer susceptibility to cancer. We shall take these studies forward by characterising the natural history of the syndromes in large European materials. Simultaneously, we shall perform functional studies to elucidate the cellular events induced by these defects by systematic biology approaches including functional studies in cell lines, model organisms, and transcription profi ling of TCAC defi cient and profi cient tumours and models. TCAC defect-associated expression patterns will be utilised to examine other cancer types for such defects. We have evidence that modifying genes play a key role in TCAC defect-associated tumourigenesis and candidate regions have been identifi ed. Following gene identifi cation, the possible role of these modifi ers in low penetrance cancer predisposition in the general population will be examined. The rationale to form this consortium is simple and strong. The consortium brings together the key European cancer researchers studying TCAC-associated tumourigenesis. Studying the tumourigenic eff ects of FH and the diff erent units of SDH separately would be ineff ective, and formation of the consortium will ensure that Europe will maintain the initiative in this new and exciting fi eld of research. The deliverables arising from the work packages will contribute to the common goals; prevention of TCAC-associated cancers and learning the lessons these lesions can teach to cancer research. BIOLOGY 77 Aim The two key tasks to achieve this project’s objective are: • characterising the natural history and prevalence of TCAC-defi cient cancers; • unravelling the molecular mechanisms driving TCACassociated tumourigenesis. Expected results The impact of the proposed research is two-fold. First, it provides a basis for cancer detection, prevention and treatment in high-risk individuals with TCAC defects. The discoveries by us and others linking TCAC defects to a high risk of tumours are so recent that even the very basic data on the natural history of the respective syndromes is missing and, without this knowledge, evidence-based measures to fi ght this novel tumour type cannot be developed. Second, the proposed research will create data on the frequency of TCAC-defi cient hereditary and sporadic cancers, and will characterise the molecular mechanisms underlying their genesis. This will be a major advancement for cancer research in general. Potential applications This project will create data for management of TCACdefi cient tumours. Diagnosis • Improved molecular diagnosis of hereditary susceptibility. • Classifi cation of tumours. Also, it will create an expression profi le-based classifi er for TCAC defi cient cancers. Management • Hereditary susceptibility: it goes without saying that an exact diagnosis of the syndromes involved is a very signifi cant factor in improving the management of the patient, and the relatives. Appropriate follow-up strategies and much more accurate genetic counselling on cancer risk will become available. • TCAC-defi cient tumours: whether hereditary or sporadic, TCAC-defi cient tumours are likely to display special biological properties which are relevant for clinical management, including response to drug treatment. We anticipate that the more detailed molecular classifi cation of tumours provided by eff orts of this proposal will considerably improve the standard care of such lesions.
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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
Page 27 and 28: • public health research coupled
Page 29 and 30: Expected results We will construct
Page 31 and 32: Potential applications Our DNA is u
Page 33 and 34: Microscopic examination of tissue s
Page 35 and 36: Pluripotent embryonic stem cells ar
Page 37 and 38: • Decryption of the leukaemia cel
Page 39 and 40: • identifi cation of molecular ta
Page 41 and 42: A B C LT-HSC CSC The Cancer Stem Ce
Page 43 and 44: X-ray diff raction of target drug c
Page 45 and 46: using pathway-specifi c reporter ce
Page 47 and 48: Keywords | Kinases | pediatric panc
Page 49 and 50: Keywords | Lymphangiogenesis | angi
Page 51 and 52: Keywords | Breast cancer | metastas
Page 53 and 54: Keywords | Mitosis | phosphorylatio
Page 55 and 56: Keywords | Therapy | genome | telom
Page 57 and 58: Keywords | Multiple myeloma | cance
Page 59 and 60: Keywords | p53 tumour suppressor |
Page 61 and 62: Development of eff ective anti-canc
Page 63 and 64: Coordinator Patrick A. Curmi INSERM
Page 65 and 66: Drosophila as a model system for tu
Page 67 and 68: Normal cell growth and epithelial l
Page 69 and 70: effi ciently with cancer cell proli
Page 71 and 72: A high-throughput assay of transcri
Page 73 and 74: Coordinator Ewa Sikora Nencki Insti
Page 75 and 76: Expected results The SIROCCO consor
Page 77: Keywords | Epigenetics | gene regul
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
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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
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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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