Cancer Research - Europa

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Coordinator Kari Alitalo Centre of Excellence in Molecular/<strong>Cancer</strong> Biology Biomedicum Helsinki University of Helsinki Helsinki, Finland kari.alitalo@helsinki.fi Partners Anne Eichmann Institut National de la Santé et de la Recherche Médicale Paris, France anne.eichmann@college-de-france.fr Per Lindahl Göteborg University Göteborg, Sweden per.lindahl@wlab.gu.se Dontscho Kerjaschki Medical University Vienna Klinisches Institut fuer Klinische Pathologie Vienna, Austria dontscho.kerjaschki@meduniwien.ac.at Elisabetta Dejana IFOM Fondazione Istituto FIRC di Oncologia Molecolare Milan, Italy elisabetta.dejana@ifom-ieo-campus.it Gerhard Christofori Institute of Biochemistry and Genetics Dept. of Clinical-Biological Sciences University of Basel Basel, Switzerland gerhard.christofori@unibas.ch 48 Hellmut Augustin KTB Tumorforschungsgesellschaft mbH Dept. of Vascular Biology and Angiogenesis <strong>Research</strong> Freiburg, Germany augustin@tumorbio.uni-freiburg.de Lena Claesson-Welsh Dept. of Genetics and Pathology Uppsala University Vascular Biology Unit Uppsala, Sweden lena.claesson-welsh@genpat.uu.se Miikka Vikkula BCHM/Christian de Duve Institute of Cellular Pathology Laboratory of Human Molecular Genetics Brussels, Belgium vikkula@bchm.ucl.ac.be Peter Carmeliet Centre for Transgene Technology and Gene Therapy Flanders Interuniversity Institute for Biotechnology University of Leuven Leuven, Belgium peter.carmeliet@med.kuleuven.ac.be Seppo Ylä-Herttuala A.I. Virtanen Instituutti University of Kuopio Kuopio, Finland seppo.ylaherttuala@uku.fi Mattias Kalén AngioGenetics AB Medicinaregatan Gothenburg, Sweden mattias.kalen@angiogenetics.se Markku Jalkanen Lymphatix Oy (Lymphatix Ltd) Helsinki, Finland markku.jalkanen@faronpharmaceuticals.com Christer Betsholtz Karolinska Institutet Laboratory of Vascular Biology Division of Matrix Biology Dept. of Medical Biochemistry and Biophysics Stockholm, Sweden christer.betsholtz@ki.se Project number LSHG-CT-2004-503573 EC contribution € 9 000 000 Duration 60 months Starting date 01/05/2004 Instrument IP Project website www.lymphomic.org CANCER RESEARCH PROJECTS FUNDED UNDER THE SIXTH FRAMEWORK PROGRAMME
Keywords | Breast cancer | metastasis | gene profi ling | organ-specifi c metastasis | MetaBre Molecular mechanisms involved in organ-specifi c metastatic growth processes in breast cancer Summary Breast cancer is often accompanied by the development of metastases, particularly in bone, liver, lung, brain or lymph node tissues. The metastases cause a range of symptoms ultimately leading to increased morbidity and mortality. Metastasis is a complex multi-step process and little is known about the molecular mechanisms that direct metastases to form in certain organs in diff erent patients. MetaBre will analyse diff erential gene and protein expression in primary breast cancers and metastases in order to identify the molecules involved in organ-specifi city. These will be investigated as potential novel therapeutic targets and biomarkers for prognosis of organ-specifi c metastasis in breast cancer patients. MetaBre has research activities aimed at: • gene profi ling and proteomic analysis to identify new molecular targets; • functional analysis of new targets in in vitro and in vivo models; • mechanisms of angiogenesis and invasion; • organ-cancer cell interactions; • development of new pharmacological therapies and diagnostic techniques; • preliminary clinical trials. MetaBre will develop in vivo models for validation of molecular targets and screening of therapeutic molecules. Metastases will be detected in vivo with optical imaging of cancer cells transfected with optical reporter genes, and magnetic resonance techniques. Problem More than 200 000 women are diagnosed in Europe every year with breast cancer. The lifetime risk of developing breast cancer is currently one in ten and the disease is the leading cause of death in women between the ages of 35 and 55. There has been considerable success in the treatment of breast cancer in recent years, if detected in its early stages. However, breast cancers are prone to metastasise and cause secondary lesions in bone, liver, lung, brain and lymph nodes. Once solid metastatic tumours are established, the likelihood of complete remission reduces and, depending on the site of metastases, they can cause considerable pain and increased mortality. BIOLOGY Metastasis in breast cancer is a complex multi-step process. Genetic changes in tumour cells give rise to aggressive metastatic cells, and their subsequent development in specifi c sites depends on a web of cellular and matrix interactions within each organ microenvironment. Understanding the key molecular mechanisms of these metastatic processes can lead to improvements in the prognosis and treatment of breast cancer patients. Aim MetaBre aims to discover new gene and protein markers, which can be used for diagnosis as a signature of metastasis to specifi c organs, and also be targeted for therapy. To achieve this, the partners will analyse samples of breast primary tumours and metastases, with due care of the ethical aspects, as well as established breast cancer cell lines. MetaBre will also study genes and molecules that are already suspected of involvement in metastasis. This builds on previous work of the partners and will enhance understanding of the role of these molecules in metastasis, as well as identifying new opportunities for development of therapies and diagnostic methods. Expected results MetaBre aims to generate the following results: • identifi cation and characterisation of molecular signatures including serum biomarkers for diagnosis of organ-specifi c metastatic potential in breast cancer; • identifi cation of new molecular targets for inhibition of angiogenesis, invasion of metastatic cells, and growth of metastases in specifi c organs; • development of a catalogued collection of primary tumours, metastases and related samples; • development of new clinically relevant in vitro and in vivo models for study of metastatic disease in breast cancer; • development of diagnostic techniques and identifi cation of at least one novel pharmacological therapy. Potential applications The project will identify novel molecular mechanisms that may be targeted for therapy of metastatic disease in breast cancer. The genes related to organ-specifi c metastasis may be used as biomarkers for stratifi cation of breast cancer patients according to the risk of developing metastases, either through gene expression microarray analysis of primary tumours, or through measurement of those markers present in serum. 49
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 and 14: p53 activators ASPP Partner 5 NFkap
Page 15 and 16: Keywords | Angiogenesis | vasculoge
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: Keywords | Lymphangiogenesis | angi
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
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MolDiag-Paca Novel Molecular Diagno
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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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