Cancer Research - Europa

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Coordinator Giovanni Blandino Translational Oncogenomics Unit Molecular Medicine Department Regina Elena Cancer Institute Via Elio Chianesi, 53 Rome, Italy blandino@ifo.it Partners Matthias Dobbelstein Georg-August-Universität Göttingen Göttingen, Germany Ygal Haupt The Lautenberg Center for General and Tumour Immunology The Hebrew University – Hadassah Medical School Jeruslem, Israel Guido Kroemer INSERM Institut National de la Santé et de la Recherche Médicale Paris, France Xin Lu Tumour Suppressor Group Ludwig Institute for Cancer Research London, United Kingdom Karen Voudsen The Beatson Institute for Cancer Research Tumour Suppressor Laboratory Glasgow, United Kingdom 12 Varda Rotter/Moshe Oren Weizmann Institute of Science Molecular Cell Biology/Biology Rehovot, Israel Nicholas B. La Thangue University of Oxford Oxford, United Kingdom Gerry Melino Medical Research Council Leicester, United Kingdom Jiri Bartèk Danish Cancer Society Dept. of Cell Cycle and Cancer Institute of Cancer Biology Danish Cancer Society Copenhagen, Denmark Massimo Levrero Fondazione Andrea Cesalpino Laboratory of Gene Expression Rome, Italy Aart Gerrit Jochemsen Dept. Molecular and Cell Biology Tumour Suppressor Group Leiden University Medical Center Leiden, The Netherlands Galina Selivanova Karolinska Institute Dept. of Laboratory Medicine Stockholm, Sweden Gianni Del Sal Università degli Studi di Trieste Dipartimento di Biochimica Biofisica e Chimica delle Macromolecole Trieste, Italy Richard Iggo University of St. Andrews St. Andrews, United Kingdom Wolfgang Deppert Heinrich-Pette-Institut für Experimentelle Virologie und Immunologie an der Universität Hamburg Dept. of Tumour Virology Hamburg, Germany David Lane/Sonia Lain University of Dundee Dept. of Surgery and Molecular Oncology Nethergate Dundee, United Kingdom Simona Greco Biotecgen s.r.l. Dept. of Biological Sciences Institute of Physiology Lecce, Italy Cristina Fregonese INNOVA spa Tecnopolo Tiburtino Rome, Italy Roberto Mantovani GeneSpin srl SME Milan, Italy Project number LSHC-CT-2004-503576 EC contribution € 6 000 000 Duration 60 months Starting date 01/12/2004 Instrument IP Project website www.europeire.it/ Activep53/intro.htm CANCER RESEARCH PROJECTS FUNDED UNDER THE SIXTH FRAMEWORK PROGRAMME
Keywords | Angiogenesis | vasculogenesis | blood vessels | tumour | endothelial cells | clinical trials | microarrays | proteomics molecular targets | ANGIOTARGETING Multidisciplinary research to explore and validate molecular targets for innovative treatments Summary Solid tumour growth depends on the recruitment of new blood vessels that will provide the cancer cells with nutrients and oxygen. The ANGIOTARGETING project intends to fi nd new targets on the tumour vasculature. The project will then defi ne these targets and develop new therapeutic strategies towards them. The apparent limited success in translating angiogenesis research into the clinic is, in our view, based on the fact that the research fi eld has been fragmented, and no standardised tools and models have been identifi ed that reliably refl ect the complexity of tumour angiogenesis mechanisms in humans. ANGIOTARGETING will identify and validate new therapeutic targets directed towards tumour vascular-matrix interactions, develop new therapeutic strategies and implement such strategies in pre- and clinical trials. The project represents a virtual research institute in Europe and consists of 14 highly competent research centres within the fi eld of angiogenesis research. To defi ne and validate new targets related to the tumour vascular transcriptome and proteome, the consortium will establish high throughput functional screening technologies for the identifi cation of novel secreted factors that regulate endothelial cell growth and survival. This includes the use of robotic platforms that will be used to identify cDNAs with specifi c cellular functions. In this project, basic science, translational research and clinical activities are strongly integrated, in order to validate defi ned targets and to develop new therapeutic principles for clinical implementation. Problem The signifi cant role of neovessel formation in health and disease has been clearly demonstrated during the last decade. The molecular mechanisms that lead to the establishment of functional blood vessels are also key factors that regulate tumour progression. Considerable eff orts have been devoted to research identifying the mechanisms that regulate the recruitment of blood vessels to tumours. Under normal conditions, the establishment of blood vessels is a highly complex and coordinated biological process. Targeting non-cancer cells that feed and drain the tumour and form channels through which tumour cells can disseminate, rather than targeting the neoplastic cells themselves, represents an approach to cancer therapy that holds particular promise because these cells are genetically stable, and therefore less likely to accumulate mutations that allow them to develop drug resistance. The fi rst meaningful clinical eff ects of antiangiogenic therapy in human cancer have recently been demonstrated. However, in spite of some highly encouraging results, most angiogenesis inhibitors, reported to suppress tumour growth in animal models, have thus far failed in human clinical trials. In our view, this refl ects that no standardised tools and models have been identifi ed that reliably refl ect the complexity of tumour angiogenesis mechanisms in humans. The successful translation of potential angiogenesis inhibitors to clinical application depends partly on the transfer of expertise from scientists who are familiar with the biology of angiogenesis to clinicians, as well as an active feedback from the clinicians to the scientists. ANGIOTARGETING aims at the identifi cation and validation of new therapeutic targets in tumour vasculature, develops new therapeutic strategies and implement such strategies in pre- and clinical trials. A strong focus on translational research and clinical implementation will convert R&D results into direct public and economic benefi ts. BIOLOGY 13 Aim The objective is the identifi cation and validation of new therapeutic targets directed towards tumour vascularmatrix interactions. Expected results • The project will increase our understanding of how tumours generate a vascular supply. • The project will develop new technologies to defi ne and validate key molecular targets that control tumour vascularisation and invasion. • The project will identify potential therapeutic targets towards the tumour vascular and invasive transcriptome and proteome. • The project will develop comprehensive bioinformatics tools for the analysis of high throughput gene and protein data from defi ned cell populations within tumours. • The project will develop state-of-the-art platforms for preclinical and clinical assessment of newly developed compounds. • The project will provide new information on how potential antivascular therapies shall be evaluated in the clinic. This includes the development of surrogate markers to evaluate therapeutic effi cacy.
Page 1 and 2: PROJECT SYNOPSES CANCER RESEARCH PR
Page 3 and 4: CANCER RESEARCH PROJECTS FUNDED UND
Page 5 and 6: TABLE OF CONTENTS FOREWORD - CANCER
Page 7 and 8: Prevention 97 EPIC 98 EUROCADET 100
Page 9 and 10: CANCER: COMBATING A COMPLEX DISEASE
Page 11 and 12: Biology Cancer is a disease ethat t
Page 13: p53 activators ASPP Partner 5 NFkap
Page 17 and 18: Keywords | Tumour-host interactions
Page 19 and 20: Keywords | Breast | metastasis | ge
Page 21 and 22: Keywords | Identifi cation of novel
Page 23 and 24: Keywords | Systems biology | modell
Page 25 and 26: 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 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 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 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
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
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 and 246:
Scientifi c Model Systems The compl
Page 247 and 248:
Performance of benchmarking exercis
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:
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