Cancer Research - Europa

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COBRED Colon and Breast cancer Diagnostics Summary COBRED aims at the discovery of colon and breast cancer biomarkers for patient follow-up (monitoring markers). COBRED will exploit the high-throughput analysis capacity of transcriptomics, proteomics and metabolomics technologies in an integrated systems biology approach and the expertise of biotech SMEs and academic partners to discover biomarker candidates. Two clinical institutes renowned for their expertise in colon and breast cancer will participate in the study with the design and execution of a prospective clinical collection and will carry out the biological and clinical validation of the effi ciency of the identifi ed biomarkers. After 3 years COBRED will deliver a set of biomarker candidates verifi ed in preclinical studies, ready for large scale clinical validation and further development for commercialization by the respective SME partners. Furthermore COBRED will have demonstrated the potential to explore consolidated data resulting from diff erent high-throughput technologies and clinical profi les with advanced data mining technologies for enhanced biomarker discovery. Although within the project scope COBRED focuses on biomarkers for follow-up diagnostics, it has the potential to evolve to an early cancer detection & screening tool. Problem Keywords | Biomarkers | colon cancer | breast cancer | follow-up diagnostics | screening | transcriptomics | genomics | proteomics | metabolomics | data mining | An apparent paradox of current cancer epidemiology is that while new therapies and diagnostics improve survival rates in common cancers, e.g. colon and breast cancer, the incidence rates are also increasing, thus the net eff ect is negative. Colorectal cancer (CRC) is the third commonest cancer type worldwide; in the year 2000 the global incidence was about 1 million, close to 10 % of all cancers, and it resulted in about 0.5 million deaths, equalling of about 8 % of all cancer mortality. Breast cancer (BC) is the most common cancer in Western women. In these patients, it is not the primary tumour, but its distant metastases that are the main cause of mortality. The yearly incidence rate is over 0.5 million (630 000 new breast cancer cases) that results in about 0.2 million deaths. Recently, the rates of metastasis and mortality in BC patients have decreased as a result of early diagnosis by mammographic screening and the implementation of systemic adjuvant therapy similarly to CRC. There is ample, but ‘only’ circumstantial evidence that derives from survival data of patients with early stages of cancer, suggesting that earlier diagnosis would allow 10-20 % survival rates improvement. In fact, the potential benefi ts of early CRC and BC diagnosis are so high that a wide range of community and governmental eff orts have been implemented for population wide screening. Biomarkers are substances found in the blood, other body fl uids (e.g. urine) or tissues that alone or in combination may signal the presence of cancer or the risk for cancer. Diagnostics based on biomarkers have the potential to signifi cantly improve current cancer diagnostic means, providing a higher sensitivity (i.e. much smaller tumours can be detected), easier and faster and at a much lower cost. Biomarker discovery and validation, similarly to drug discovery and validation, is a long process with high rate (60-80 %) of attrition of candidate biomarkers along the major steps of qualifi cation that ultimately ends in the approval by the Food and Drug Administration (FDA) in the US and the European Agency for the Evaluation of Medicinal Products (EMEA) in the EU. Often, seemingly good candidates that have been identifi ed and found valuable in one study do not show the expected predictive values in the second study. In fact, the number of new diagnostics approved per year is decreasing in sharp contrast to the intensifying biomarker discovery eff orts. Thus, despite having the highest potential value in numbers, COBRED choose not to pursue the discovery of screening markers because of economic and logistic impracticalities of a large scale screening-marker validation in BC and CRC. Instead, we focus on the second largest clinical need, the improvement of patient follow up, by the discovery of monitoring markers, which are expected to report relapse, metastasis and minimal residual disease at earlier stages, which are more amenable to surgical and chemotherapy treatment, and more likely to improve cancer patient survival. Aim The specifi c RTD objectives are to: • design a clinical protocol for prospective clinical BC and CRC collections that fi t the needs of the 3 high-throughput screening technologies used: transcriptomics, proteomics and metabolomics; • identify biomarker candidates (metabolites, proteins, PBL derived mRNAs) capable to detect and assess the status of minimal residual disease, metastases and recurrence after surgery and chemotherapy; • develop a centralized database to integrate the data generated by the 3 technology platforms with the anatomo-clinical information of the clinical collections; • discover biomarkers with better specifi city and sensitivity using across-platform advanced data-mining techniques on the combined data from the consolidated database; • validate the biological relevance and diagnostic potential of the identifi ed biomarkers by testing their specifi city on tissue arrays and in relevant preclinical models. 116 CANCER RESEARCH PROJECTS FUNDED UNDER THE SIXTH FRAMEWORK PROGRAMME
Expected results Specifi c project results will include: • sets of biomarkers (gene signatures, proteins, metabolites or a combination of these) that will be considered clinically relevant for early diagnosis of primary BC and CRC and relapses; • central repository system hosting the results from the technological platforms and the relevant clinical data; • prospective clinical collection of BC and CRC; • clinical validation for the diagnostic potential of subsets of the identifi ed biomarkers in comparison to existing biomarkers and to currently available imaging techniques; • preclinical models for the biomarker evaluation and biological studies. Potential applications Diagnostic kit for the detection of cancer recurrence and metastasis, with the longer term goal to develop early cancer detection tests amenable for population screening. Coordinator Mariana Guergova-Kuras BioSystems International 4 rue Pierre Fontaine 91058 Evry cedex, France mariana.kuras@biosys-intl.com Partners Andras Guttman University of Innsbruck Horváth Laboratory of Bioseparation Sciences Institute of Analytical Chemistry and Radiochemistry Leopold-Franzens University Innrain 66, 6020 Innsbruck, Austria andras.guttman@uibk.ac.at Klaus Weinberger Biocrates BIOCRATES Life Sciences GmbH Innrain 66/2 6020 Innsbruck, Austria klaus.weinberger@biocrates.com EARLY DETECTION, DIAGNOSIS AND PROGNOSIS Fabienne Hermitte Ipsogen Luminy Biotech Entreprises Case 923 – 163, av. De Luminy 13288 Marseille Cedex, France Hermitte@ipsogen.com Xavier Sastre-Garau Institut Curie Cell Biology Department Department Translational <strong>Research</strong> 26 rue d’Ulm, 75248 Paris cedex 05, France xavier.sastre@curie.net David Malka Institut Gustave-Roussy 39 rue Camille Desmoulins 94805 Villejuif Cedex, France david.malka@igr.fr Laszlo Fesus University of Debrecen Department of Biochemistry and Molecular Biology Medical and Health Science Center Egyetem Ter 1. 4010 Debrecen, Hungary fesus@dote.hu Jaak Vilo University of Tartu Ülikooli 18 50090 Tartu, Estonia jaak.vilo@ut.ee Bruno Cucinelli Arttic SA 58A rue du dessous des berges 75013 Paris, France cobred@arttic.fr Project number LSHB-CT-2007-037730 EC contribution € 2 985 102 Duration 36 months Starting date 01/03/2007 Instrument STREP Project website www.cobred.eu 117
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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
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 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
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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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HOW TO OBTAIN EU PUBLICATIONS Our p
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