KI-NA-24-042-EN-C Cancer research

This booklet gives a short overview of cancer research projects that have been funded sofar under the European Union’s Seventh Framework Programme (FP7; 2007-2013) – the EU’s main instruments for funding research in Europe.

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Cancer research EU Funding (2007-2009)

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Cancer researchEU Funding

(2007-2009)

Edited by Jan-Willem van de Loo

DIRECTORATE-GENERAL FOR RESEARCH

2009 MEDICAL AND PUBLIC HEALTH RESEARCH EUR 24042 EN

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Cancer researchEU Funding

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Table of contents

03K 6

ADAMANT 7

ANTICARB 8

AUTOCAST 9

CANCERDIP 10

CANCERPATHWAYS 11

CHIBCHA 12

COGS 13

DECanBio 14

DIRECT 15

EPOC 16

EUCAAD 17

EUROCOURSE 18

FLUODIAMON 19

GENICA 20

GENINCA 21

INFLA-CARE 22

LOULLA&PHILLA 23

METAcancer 24

METAFIGHT 25

METOXIA 26

MICROENVIMET 27

MISMATCH2MODEL 28

NANOPHOTO 29

ONCOMIRS 30

OPCARE9 31

O-PTM-BIOMARKERS 32

PRISMA 33

PROACTIVE 34

PROMARK 35

PROSPER 36

SFMET 37

SKINSPECTION 38

TARCC 39

TELOMARKER 40

TuMIC 41

UROMOL 42

ZF-CANCER 43

03K

Oral Off-patent Oncology Drugs for Kids

There is an urgent need for appropriate oral formulations of anticancer drugs for the

treatment of paediatric malignancies in children. The goal of the O3K consortium is to

develop oral liquid formulations of cyclophosphamide and temozolomide, important

chemotherapeutics which have been identifi ed in the list of paediatric needs by

EMEA (EMEA/197972/2007). Both off -patent drugs are widely used orally for the

treatment of childhood cancer. However, the currently available tablets (cyclo-

phosphamide) and capsules (temozolomide) are not suitable for use in a paediatric

setting, particularly in infants and young children, as it is often impractical for them

to be swallowed. This is a major health concern since, as a consequence, these

children do not readily have direct and safe access to these curative drugs. The

NODS® technology represents an innovative oral drug delivery system for drinkable

products for children. Drug entrapment in NODS® particles provides gastroprotection,

stabilisation, chemical protection of labile compounds and taste masking. The O3K

project will conduct the pharmaceutical, clinical and pharmacological studies

required for the development of these oral liquid formulations and, on completion,

will fi le dossiers for both products containing the data required for application for a

Paediatric Use Marketing Authorisation (PUMA). The EMEA Scientifi c Advice is already

ongoing. O3K will provide access to curative drugs for all children with cancer,

improving compliance, ensuring safety for both patient and environment, and

allowing the development of essential ambulatory treatments. In accordance with

ICH guidelines, the development of these agents will lead to improved quality and

safety of paediatric drug formulations. The O3K project involves nine partners –

including fi ve institutions and three SMEs providing expertise in clinical and

pharmacological research relating to paediatric oncology, along with one parents

organisation – from three European Member States (UK, IT and FR).

Coordinator Dr Gilles VassalInstitut Gustave Roussy, Villejuif, France

e-mail [email protected]

EC contribution € 5 958 419

Start date 01/09/2008

Duration 36 months

Project website In preparation

6

ADAMANT

Antibody Derivatives as Molecular Agents for Neoplastic Targeting

The selective delivery of bioactive agents – cytotoxics, radionuclides, cytokines – at

the tumour site, while sparing normal tissues, represents one of the most promising

avenues for the development of anticancer therapies with unprecedented effi cacy

and tolerability. Monoclonal antibodies represent the preferred vehicle for the

targeted delivery of bioactive agents to cancer sites, as they can display a preferential

accumulation in primary and metastatic tumour lesions within a few hours of

intravenous administration. Certain monoclonal antibody derivatives can remain on

the neoplastic mass for several days, thus permitting the slow release of potent

cytotoxics or the continuous action of bioactive agents such as cytokines or

therapeutic radionuclides. The ADAMANT Project aims to generate anticancer agents

of superior quality that rely on the antibody-based delivery of cytotoxics,

radionuclides or immunostimulatory cytokines to either vascular tumour antigens or

to tumour cell membranes. While clinically validated antibodies will allow the rapid

development of therapeutic strategies based on novel antibody derivatives,

innovative perfusion-based chemical proteomic technologies will facilitate the

discovery of accessible and abundant tumour-associated antigens, ideally suited for

the targeted delivery of bioactive agents to cancer sites. Imaging methodologies will

guide the consortium in the selection of antigens, antibodies and therapeutic agents

with optimal pharmacokinetis and pharmacodynamics. Finally, therapy studies in

tumour-bearing mice, featuring the use of antibody derivatives in combination with

other anti-cancer drugs (cytotoxic, biological, vascular disrupting agents), will

provide insights into how best to translate the results of the ADAMANT project into

clinical development.

Coordinator Dr Raff aella GiavazziIstituto di Ricerche Farmacologiche "Mario Negri", Milano, Italy




Duration 36 months

Project website http://www.adamant-fp7.eu/

CANCER RESEARCH EU FUNDING (2007-2009) 7

ANTICARB

Monoclonal Antibody-targeted Carbon Nanotubes against Cancer

ANTICARB attempts to exploit the advantages off ered by a novel nanotechnology

platform – carbon nanotubes – and apply them to a clinically established therapeutic

modality – targeted antibody therapy – for the creation of hybrid nanotechnology-

based monoclonal antibody targeted cancer therapeutics. ANTICARB combines two

emerging technologies, antibody and nanotube technology, in a way that will allow

safe development of antibody-nanotube conjugates and explore their swift

translation into a clinical oncology setting. By combining proven, clinically used, anti-

cancer agents – antibodies – with a novel nanotechnology-based platform made of

advanced nanomaterials, ANTICARB aims to enhance the therapeutic potency of the

antibody and establish a new paradigm for oncology therapeutics. The ability of

carbon nanotube technology to transport antibodies into the tumour cell cytoplasm

may lead to validation of specifi c intracellular targets for oncology. This objective will

be reached by adopting a multidisciplinary approach and by bringing together

expertise from the fi elds of drug delivery, molecular biology, chemistry, engineering,

pharmacology and toxicology. The proposal capitalises on this industry-academia

multidisciplinary and fully integrated team whose expertise ranges from advanced

biotech to sophisticated nanotechnology.

Coordinator Dr Kostas KostarelosThe School of Pharmacy, University of London, London, UK




Duration 36 months

Project website http://cordis.europa.eu/fetch?CALLER=FP7_PROJ_EN&ACTION=D&DOC=447&CAT=PROJ&QUERY=011aa1a0aaaf:2621:015d7d2c&RCN=86759

8

AUTOCAST

Automatic Cancer Screening based on Real-time PCR

Cancer accounts for nearly one-quarter of deaths in the developed world, exceeded

only by heart diseases. One of the key strategies in cancer prevention is early

diagnosis through cancer screening programmes. Estimates of the premature

deaths that could have been avoided through cancer screening vary from 3% to 35%,

depending on a variety of assumptions. Beyond the potential to reduce mortality,

screening may also reduce cancer morbidity, since treatment for earlier-stage

cancers is often less aggressive than that for more advanced-stage cancers. Currently

many of these screening programmes produce false negative results, as well as long

time delays in obtaining the results, thus increasing patient anxiety and lapses in

starting treatments. This project will develop a novel rapid real-time PCR/probe

technology in a microarray biochip format, with the corresponding automated

instrumentation for use as a rapid point-of-care diagnostic device. Cervical cancer

and its associated virus, the human papillomavirus, is the model system which will

be used to develop this automated cancer screening technology. The real-time PCR

technology will permit detection of panels of multiple biomarkers in a single PCR

reaction. The partners have already developed prototype technology which partly

demonstrates a microarray approach to real-time PCR and the project will build on

this, providing the innovation needed to transform a promising technology into an

integrated system suitable for practical use at point-of-care setting. The consortium

includes four research institutes and two SMEs which combine extensive experience

with real- time PCR and microarray technologies and the motivation to commercialise

results. In addition, Partner 7 will act as the end-user, validating the system in a

clinical setting.

Coordinator Dr Csaba JeneyGenoid Molekularbiologiai Kutato, Gyarto Es Egeszsegugyi Szolgalato KFT, Budapest, Hungary




Duration 36 months



CANCERDIP

The Use of Methylated DNA Immunoprecipitation MeDIP in Cancer for better Clinical Management

Aberrant DNA methylation is the most common molecular lesion of the cancer cell.

Neither gene mutation nor cytogenetic abnormalities are as common in human

tumours as DNA methylation alterations. The stability of our genome and correct

gene expression is maintained to a great extent through a perfectly preestablished

pattern of DNA methylation and histone modifi cations. In cancer this idealistic

scenario breaks down due to an interesting phenomenon where the regulatory

regions (CpG islands) of certain tumour suppressor genes become hypermethylated,

inactivating the gene as a consequence, whilst a wave of hypomethylation occurs in

the genome. Indeed, CpG island promoter hypermethylation has a tumour-type-

specifi c pattern, where each gene tends to be methylated in the cancer cells driven

from a particular tissue, but not from others. It is also widely accepted that the

multiprotein complex associated with the methylated DNA is also crucially involved

in the repression of gene expression. Another aspect crucial for the interest of

epigenetics in cancer is that promoter hypermethylation of the CpG island of

tumours’ suppressor genes occurs early in tumorigenesis. Furthermore, it has been

extensively reported that CpG promoter hypermethylation can be used as a predictor

of cancer behaviour and of response to treatment. This characteristic makes

promoter hypermethylation, combined with the epigenetic associated proteins

profi le, a potential biomarker for early detection of cancer and for the individualisation

of cancer treatment. The project will use a novel technique based on chromatin

immunoprecipitation, the Methylated DNA Immunoprecipitation (MeDIP) technique,

which will readily produce an epigenomic profi le to personalise cancer treatment

and facilitate tumour diagnosis, prognosis and monitoring.

Coordinator Dr Manel EstellerBellvitge Institute for Biomedical Research,Barcelona, Spain




Duration 36 months

Project website http://www.cancerdip.eu/

10

CANCERPATHWAYS

Developmental Molecular Pathways in Drosophila as a Model for Human Cancer

Cancer is often characterised as a disease of signal transduction pathways, since it is

often associated with the inappropriate activation of these pathways. Indeed, new

therapeutic approaches in cancer therapy, such as Herceptin, frequently target

signalling pathway components to revert their pathophysiological aberrations. Most

oncogenic pathways have been highly conserved throughout evolution, with

Drosophila representing a particularly powerful genetic model for the analysis of

such signalling cascades. These cancer pathways include the Wnt, Notch, Hippo and

JAK/STAT systems. The analysis of signalling pathways in Drosophila is facilitated by

the availability of a broad range of genetic tools, a completely sequenced genome,

and the availability of genome-wide collections of RNAi reagents. This project will

establish high-throughput cell-based assays for regulators of the major

developmental oncogenic signalling pathways. Cell-based assays for signalling

pathways will be screened using genome-wide RNAi and small molecule compound

libraries to identify new components, regulators and targets. Suppressor/enhancer

screens in cultured cells will be used to identify small molecular compounds that

interfere with the activity of specifi c signalling pathways, and in vivo models of

signalling pathways will be established to test the activity of drugs using

developmental and tumorogenic phenotypes. By integrating and standardising data

from the most important cancer-relevant signalling pathways and combining them

with powerful bioinformatics tools, the project expects to get highly validated

information on possible drug targets and lead substances. This collaborative project

integrates recent technological advances, such as genome-wide RNAi libraries for

cell-based and in vivo assay models that were developed by the participants, as well

as computational approaches and databases to integrate and disseminate the

information obtained during the project.

Coordinator Dr Michael BoutrosDeutsches Krebsforschungszentrum Heidelberg, Heidelberg, Germany




Duration 36 months

Project website http://www.cancerpathways.eu


CHIBCHA

Genetic study of Common Hereditary Bowel Cancers in Hispania and the Americas

Colorectal cancer (CRC) is common in both sexes, has relatively poor outcome and

has no major avoidable risk factor. Recent studies have shown that common

inherited single nucleotide polymorphisms (SNPs) can increase cancer risk. The

consortium has shown CRC risk to be associated with SNPs on chromosomes 8q24.21,

15q14 and 8q21. These variants account for <5% of the genetic risk of CRC, but will be

very important when their eff ects are added to those of other, as yet undetected,

CRC SNPs. A few genome-wide association studies (GWASs) based on populations of

European descent are attempting to identify the remaining common CRC genes.

However evidence suggests that these studies will not be large enough on their own

to detect all CRC SNPs: the risks associated with most SNPs are modest, some disease

alleles are rare at least in Europe, and many variants may lie outside the conventional

gene boundaries or haplotype blocks. The admixed Latin American population

provides an exciting opportunity to identify new CRC genes that are more tractable

to detection there or have been missed in European studies. The project will

undertake a combined GWAS and admixture mapping study for CRC predisposition

genes in 6 000 cases and 6 000 controls, and test the disease-associated variants in

3 500 cases and 3 500 controls from Europe. The project is designed primarily to

detect SNPs with eff ects in both Latin America and Europe, but also SNPs with eff ects

specifi c to Latin Americans. Eventually, it aims to develop a polymorphism panel for

predicting the risk of CRC in the general population, so that those at increased risk

can be off ered eff ective measures to prevent cancer. CRC is increasing in frequency

in Latin America and prognosis is poorer than in Europe. The project will be a focus

for education about CRC, especially in Latin America, and will also provide training for

young researchers there. The work will provide direct benefi ts to medical science

and the populations of Latin America and Europe.

Coordinator Dr Ian TomlinsonUniversity of Oxford, Oxford, UK




Duration 42 months


12

COGS

Collaborative Oncological Gene-environment Study

The overarching goal of COGS is to identify individuals with an increased risk of

breast, ovary or prostate cancer. The project will also evaluate the eff ect of inherited

genetic variation on tumour characteristics and clinical outcome by quantifying the

role of genetic and environmental/lifestyle risk in the largest data set ever generated:

in all, over 200 000 individuals will be included in the project. The consortium will use

detailed knowledge of the architecture of genetic susceptibility and interactions with

environmental/lifestyle factors to produce much more accurate individual risk

prediction and improved intervention strategies. COGS draws on a unique

opportunity to incorporate seven existing consortia, the members of which have

collaborated successfully over recent years and their results published in leading

international scientifi c journals such as Nature, Nature Genetics and Journal of the National Cancer Institute: these papers indicate that collaboration has been ongoing

and has so far been very successful. The project will also build on an existing

European Commission project, TRANSBIG, thereby adding value to the funds already

invested. Results generated by COGS will lead to an improved understanding of the

biological processes that underlie carcinogenesis and may in turn help shape new

therapeutic strategies. These results will also lead to the development of new tests

for risk prediction of breast, ovarian and prostate cancer.

Coordinator Dr Per HallKarolinska Institutet, Stockholm, Sweden




Duration 48 months



DECanBio

Novel MS-based Strategies to Discover and Evaluate Cancer Biomarkers in Urine: Application to Diagnosis of Bladder Cancer

In clinical studies, proteomics and transcriptomics allow the comparison of samples

from diff erent patients and hold special promise for the discovery of novel

biomarkers and the development of ‘personalised medicine’ approaches. However

translating recent discoveries into daily medical practice takes time and, despite

intensifi ed interest by researchers and investment, the rate of introduction of novel

biomarkers in clinical practice is extremely disappointing. The main aim of DECanBio

is to implement a strategy for protein biomarker discovery and validation relying on

state-of-the-art mass spectrometry instrumentation for the quantitative analysis of

proteins. For the fi rst time, the potential of MRM-Mass Spectrometry (MRM-MS) will

be tested in the context of a large-scale validation protocol of cancer protein

biomarkers. This analysis will be performed in parallel with the application of

miniaturised high-throughput ELISA tests for protein quantifi cation. DECanBio

strategy will be applied to issues related to bladder cancer. Specifi cally, a restricted

number of urinary protein biomarkers, enabling the detection of recurrences during

the monitoring period of patients treated for bladder tumours, will be validated. The

work will be performed in priority for the follow-up of low-grade superfi cial bladder

tumours (Ta stage) which, after initial resection (without BCG therapy), are likely to

evolve towards remission, recurrence or progression towards a high-grade tumour.

The MRM and ELISA tests developed here will aim at the high-throughput

quantifi cation of these markers in urine. Collectively, the project has the ambition to

establish a whole experimental pipeline, from the search for new bladder cancer

biomarker candidates to their thorough evaluation and validation in a clinical

environment.

Coordinator Dr Jérôme GarinCommissariat à l’Énergie Atomique, Grenoble, France




Duration 48 months

Project website http://www.decanbio.eu

14

DIRECT

DIsseminate Research funded by EC improving Treatment options for children suffering from cancer

Clear communication of research projects and their results is an essential part of

performing science with public funds. However, progress in science is often slow,

achievements of relevance to society occur in many iterative steps, and the benefi t

for the public can hardly ever be associated with a single breakthrough discovery.

While publicly funded research is increasingly accessible, complex individual fi ndings

require a more global approach to make their societal benefi ts tangible. Children

suff ering from cancer is a highly emotional issue. Research from public funds,

including the Framework Programmes, has contributed to the substantial advances

in paediatric oncology that have been instrumental in improving treatment options

and in increasing the numbers of children surviving this malignant disease. DIRECT

aims to raise the interest in, and understanding of, health research. The approach is

based on carefully selected projects in paediatric oncology and a mountaineering

event that will highlight the good physical condition of former patients. The project

will show a link between EC-funded research and the health of young people who

have recovered from cancer. This link will be documented with the help of media

professionals and communicated to the general public through the Internet,

audiovisual and print media.

Coordinator Dr Helmut GadnerSt. Anna Kinderkrebsforschung, Vienna, Austria


EC contribution € 618 000


Duration 24 months

Project website http://www.overcomingcancerwithresearch.eu/index.html


EPOC

European Paediatric Oncology off-patent medicines Consortium

Cancer chemotherapy has a key role in the successful treatment of a number of

childhood cancers. Even so, at least 20% of patients are not cured, while a signifi cant

number of those who are cured suff er debilitating toxicities. Given the high cure

rates and potential lifespan of childhood cancer survivors, it is important to minimise

the impact of potential chronic toxicities. For several of the most widely used drugs,

little is known about their pharmacokinetics and metabolism in children, particularly

very young children. Such knowledge can be used to optimise the use of

chemotherapeutic drugs, avoid toxicity and maximise the therapeutic eff ect. The

need for further research on these drugs in children is acknowledged in the Priority

List for Studies into Paediatric Medicinal Products, issued by the EMEA. Doxorubicin is

on this list and is one of the most important drugs used in the treatment of childhood

cancers. The EPOC consortium, which combines leading pharmacologists, paediatric

oncologists and regulatory organisations, aims to provide data that will guide the

optimal use of doxorubicin in the clinic, particularly in patients of under three years.

Such data will form the basis of future applications for Paediatric Use Marketing

Authorisation for doxorubicin. The project also aims to establish a European network

for future clinical pharmacology studies in children with cancer.

Coordinator Dr Alan BoddyUniversity of Newcastle, Newcastle-upon-Tyne, UK




Duration 48 months

Project website http://cordis.europa.eu/fetch?CALLER=FP7_PROJ_EN&ACTION=D&DOC=1&CAT=PROJ&QUERY=0121f79dfd08:9773:220b0a59&RCN=89715

16

EUCAAD

European Consortium for Anticancer Antibody Development

Cancer is the second leading cause of death in European countries, and one of the

most imminent health problems in the developed world. Innovative, so-called

targeted therapies are urgently needed that aim specifi cally at cancer cells or cells of

the stroma that support tumour growth. The ultimate goal of a targeted therapy is

to increase anti-tumour effi cacy with the lowest possible side eff ects. Rapid and

effi cient translation of basic scientifi c advances into reagents – allied with targeted

molecular leads for preclinical and clinical research and development based on

scientifi c rationales and state-of-the-art technologies – optimally requires an

interdisciplinary, collaborative, team-oriented approach. EUCAAD takes the form of a

virtual research institute consisting of nine research participants, including four

SMEs, devoted to the discovery and evaluation of new antibodies for therapy in

human cancers. The consortium comprises researchers from SMEs and scientifi c and

clinical centres who have gained international acclaim in this area of research, and

many of whom have worked together on previous EC-funded applications e.g.

ANGIOSTOP, EUCAPS, ESTDAB and ENACT. The consortium draws on unique expertise

in target discovery, target validation, antibody production and initiation of clinical

trials and, as part of the eff ort to translate laboratory research into viable cancer

therapies, has accumulated an extensive portfolio of intellectual property. The focus

of the grant is the development and evaluation of antibodies against new target

structures on tumour cells, and blood vessels supplying tumours, responsible for

tumour angiogenesis, progression and metastasis. Collectively, the activities of the

consortium can improve cancer treatment standards in Europe and provide

economic benefi t to European biotechnology and pharmaceutical research by

providing novel immunopharmaceuticals.

Coordinator Dr Tina Dalianis Karolinska Institutet, Nobels Vag 5, Stockholm, Sweden




Duration 48 months

Project website http://eucaad.dinstudio.se/


EUROCOURSE

Europe against Cancer: Optimisation of the Use of Registries for Scientific Excellence in research

EUROCOURSE will tackle fragmentation in the funding and usage of cancer registries

in Europe. It will do so by exploring ways to link and integrate national/regional

programmes aimed at supporting cancer registries with research carried out using

registry data. At the same time EUROCOURSE will aim to optimise the use of cancer

registration data for the amelioration of cancer control and the strengthening

of population-based cancer research in Europe. First, funding organisations will

exchange information, best practice and technical know-how in order to harmonise

the way cancer registries are funded and organised. Second, cancer registries will be

provided with the infrastructure necessary to harmonise their data through the

exchange of technical know-how, best practices and the development of

recommendations. Additionally, the process of data collection will be streamlined to

provide comparable, accurate and timely statistics at the European level. The

inclusive approach adopted by EUROCOURSE will culminate in the First European

Cancer Summit which will bring all the stakeholders in the cancer control community

in Europe – funders, researchers and other interested parties – around one table for

the fi rst time, in order to sketch out the future of European cancer registration in

cancer control. The project will expand as a direct consequence of these planned

activities and will therefore have a major and sustained impact on cancer control and

research in Europe.

Coordinator Dr Jan-Willem CoeberghStichting Integraal Kankercentrum Zuid, Eindhoven, The Netherlands




Duration 36 months

Project website http://cordis.europa.eu/fetch?CALLER=FP7_PROJ_FR&ACTION=D&DOC=20&CAT=PROJ&QUERY=011fa3ec751c:e3a0:0aa5b383&RCN=89690

18

FLUODIAMON

Ultra-high Resolution and ultra-sensitive Fluorescence Methods for objective sub-cellular Diagnosis of early Disease and Disease Progression in Breast and Prostate Cancer

The overall objective of this proposal is to develop and validate a quantitative,

minimally invasive diagnostic tool for early and conclusive detection, diagnosis and

monitoring of disease and disease progression in breast and prostate cancer. A

methodology will be developed, using a combination of what are probably the most

exciting recent advances in the fi eld of light microscopy, to achieve fl uorescence-

based optical imaging of individual sample cells. It includes advances which will take

the spatial resolution far beyond the fundamental limits of optical resolution and

sensitivity down to an ultimate single-molecule level, with multi-parameter

detection schemes signifi cantly increasing the fl uorescence information by which

these cellular images are analysed. Apart from detecting and identifying tumour

markers in the samples, tumour-specifi c spatio-temporal molecular distributions

within the intact sample cells will be exploited. This is, to date, an almost unexploited

dimension of diagnostic information. By combining and supporting these novel

optical methods with state-of-the-art affi nity molecule biotechnology, tumour

biomarkers, fl uorophore chemistry and bioinformatic validation tools, all possible

means will be exploited to extract a maximum amount of information out of very

small amounts of sample material. The project accordingly expects that an improved,

early and reliable diagnosis of breast and prostate cancer will be possible from

amounts of sample material small enough to permit a minimally invasive procedure

such as Fine-Needle Aspiration (FNA). In addition, thanks to this minimally invasive

sampling, serious related side-eff ects such as seeding and spread of cancer cells can

be completely avoided. Given the high incidence of breast and prostate cancer, and

the utmost importance of an early and conclusive diagnosis for the prognosis of

these diseases, the relevance of this project cannot be overestimated.

Coordinator Dr Jerker WidengrenKTH Royal Institute of Technology, Kungliga Tekniska Högskolan, Stockholm, Sweden




Duration 42 months

Project website http://www.biomolphysics.kth.se/fl uodiamon/


GENICA

Genomic Instability in Cancer and Precancer

Genomic instability is a characteristic of practically all human cancers. Recent results

generated by members of this consortium suggest that signs of genomic instability

are evident from the very beginning of human cancer development, even in

precancerous lesions. In these early lesions, the genomic instability primarily eff ects

specifi c genomic loci, called common fragile sites. Because common fragile sites are

very sensitive to perturbations in DNA replication, it is suggested that cancer

development from its very beginning is associated with DNA replication stress. A

separate set of observations has focused on telomeres and shows that short

telomeres mimic DNA ends, activate the DNA damage checkpoint, and promote

genomic instability and cancer development. The project will study the role of DNA

replication stress and short telomeres in driving genomic instability, particularly in

human precancerous lesions. Studies will investigate the most common forms of

cancer in the EU and will benefi t from access to some of the largest databases of

cancerous and precancerous lesions in Europe. Genomic instability will be explored,

using high-resolution genomic arrays, and the data will be correlated with clinical

information on tumour progression. Analysis of proteins and genes involved in the

cellular response to DNA replication stress and short telomeres will also be explored,

using high throughput and targeted approaches, and will be used to identify novel

targets for cancer therapy.

Coordinator Dr Thanos HalazonetisUniversité de Genève, Geneva, Switzerland




Duration 36 months

Project website http://genica.unige.ch

20

GENINCA

Genomic Instability and genomic Alterations in pre-cancerous Lesions and/or Cancer

GENINCA will address two tumour entities, in respect of which the consortium has

access to pre-malignant lesions and in which genomic instability is a common

feature: colorectal and liver cancer. Colorectal cancer amounts to 13.2% of all incident

cases of cancer, the second most common form of cancer, surpassed only by lung

cancer (13.3%). Liver cancer accounts for about 2% of total cancers: however the most

common liver cancer, hepatocellular carcinoma (HCC), is among the most lethal

forms of cancer and its incidence in Europe has been steadily rising over recent

decades. GENINCA, which is a collaborative study by eight academic and three

industrial partners from fi ve European countries, will explore pre-cancerous and

cancer lesions of these two tumour entities and their respective microenvironments.

As the recent identifi cation of human colon-cancer-initiating cells by one of our

academic members paves the way for completely new strategies for studying the

mechanisms of tumorigenesis, a particular focus of this proposal will be the detailed

characterisation of these cancer-initiating stem cells. At present, it is still a matter of

debate as to which genomic changes are already present in precursor lesions and

whether these lesions already show genetic instability. The project will therefore

address the occurrence of genomic instability and explore its underlying

mechanisms, especially in pre-cancerous and early cancer lesions. This will be

greatly facilitated by in vivo endomicroscopy approaches, sophisticated animal

models and large-scale genomic and proteomic analyses. GENINCA will also include

an in-depth analysis of the corresponding microenvironments. As this represents a

translational research eff ort, the project expects to identify markers for novel

therapeutic and/or preventative strategies, as well as facilitate tumour diagnosis,

prognosis and monitoring.

Coordinator Dr Michael SpeicherMedizinische Universität Graz, Graz, Austria




Duration 36 months

Project website http://www.geninca.eu/


INFLA-CARE

Understanding Inflammation-associated Tumorigenesis for the rational Design of novel anti-cancer therapeutic Strategies

Epidemiological and experimental evidence supports a link between chronic

infl ammation and cancer and indicates a role for infl ammatory cells in the initiation,

progression and metastasis of malignancy. The objective of the INFLA-CARE

collaborative integrated project is to structure a European collective of scientifi c and

technological excellence in the fi eld of infl ammation and cancer, in order to capitalise

on available expertise and develop eff ective anti-infl ammatory strategies and novel

agents for cancer prevention and treatment. The project will specifi cally seek to

identify molecular and cellular targets for cancer therapy through the development

and systematic study of state-of-the-art preclinical models of infl ammation-driven

cancer. By mobilising the research experience and technological capacities of the

network participants, the programme will accelerate the translation of knowledge

obtained from basic research into new diagnostic and therapeutic strategies to be

used for the detection, prevention and improved management of several types of

human cancer. INFLA-CARE will also ensure the enhancement of scientifi c excellence

and dissemination of knowledge beyond the network, by encouraging innovation

and the transfer of know-how and by raising public understanding of scientifi c

and health issues. The impact of the programme is expected to be multi-dimensional

(i.e. scientifi c, educational and innovation-related), enhancing European competi-

tiveness and addressing major scientifi c issues and societal needs.

Coordinator Dr Aristides EliopoulosUniversity of Crete, Heraklion, Greece




Duration 48 months

Project website http://cordis.europa.eu/fetch?CALLER=FP7_PROJ_EN&ACTION=D&DOC=11&CAT=PROJ&QUERY=01207614dc6e:7337:26e29e58&RCN=89946

22

LOULLA&PHILLA

Development of 6-mercaptopurine and methotrexate oral liquid Formulations for the Maintenance Treatment of Acute Lymphoblastic Leukæmia in Children

Only for Children Pharmaceuticals (O4CP), a French Small and Medium-size Enterprise

(SME) developing drugs for children, is the coordinator of a multinational,

multidisciplinary and complementary consortium composed of highly qualifi ed

organisations and acclaimed clinicians in paediatric hematooncology. The consortium

features an integrated range of competencies – clinicians, paediatricians, pharmaco-

kineticists, pharmacists, manufacturers, engineers, regulatory and ethical experts –

capable of implementing a paediatric drug development from design to market.

O4CP will undertake the non-clinical and clinical development of methotrexate and

6-mercaptopurine oral liquid formulations adapted for maintenance treatment of

paediatric acute lymphoblastic leukaemia, with the crucial objective of making these

adapted formulation available by 2011 at the latest. Methotrexate and 6-mercapto-

purine are on the EMEA Priority List of off -patent medicinal products drawn up by

the Paediatric Working Party of the Agency in June 2007. On September 2007, EMEA’s

COMP Committee granted orphan status to methotrexate (oral liquid) and

6-mercaptopurine (oral liquid).

Coordinator Dr Vincent GrekOnly For Children Pharmaceuticals, O4CP, Paris, France




Duration 36 months

Project website http://www.o4cp.com/


METAcancer

Identification and Validation of new Breast Cancer Biomarkers based on Integrated Metabolomics

Breast cancer, the most common cancer in women, is the focus of attempts to

identify predictive molecular biomarkers. In contrast to transcriptomics, the changes

in metabolite levels associated with tumour development and progression have not

been investigated to any major extent so far: metabolomics is defi ned as the study

of all metabolites in a cell, tissue or organism, and the metabolome is regarded as

the amplifi ed output of a biological system. The originality of the METAcancer

approach lies in the fi rst-time application of combined technologies for metabolic

profi ling to the large-scale analysis of patient samples in the fi eld of translational

research in breast cancer. The project – based on a large tumour biobank as well as

on previous investigations by the consortium partners – will test the hypothesis that

alterations in the level of metabolites can be used to provide a molecular classifi cation

of breast cancer and to identify new prognostic and predictive biomarkers. It will use

three diff erent metabolic profi ling technologies – GC-MS, NMR and LC-MS – to

maximise the coverage of the breast cancer metabolome, and will apply advanced

strategies to identify individual metabolites. METAcancer’s integrated data-mining

approach combines metabolomic data obtained in the project with existing

transcriptomic data pools for the bioinformatic interpretation of cellular networks.

Using this strategy, the project will go beyond the metabolite level, and identify and

validate selected protein and mRNA biomarkers relevant to metabolic alterations.

This will result in a combined signature, consisting of metabolites as well as key

protein and mRNA markers, as a basis for a validated diagnostic system to assess

prognosis and guide targeted therapies in breast cancer.

Coordinator Dr Carsten DenkertCharite Universitatsmedizin Berlin Pathology,Berlin, Germany




Duration 36 months

Project website http://www.metacancer-fp7.eu/

24

METAFIGHT

Understanding and fighting Metastasis via Dissection of the Core Invasive Machinery

The co-operative Metafi ght project will perform functional studies to understand the

dissemination and outgrowth of metastasis through systematic analysis of the Core

Invasive Machinery contained within integrin-mediated ECM attachment structure:

this includes a large and discretely localised intracellular signalling network which

drives migration and invasion. The project strategy is based on the hypothesis that

metastatic cells arise from molecular changes that alter the primary tumour

architecture, as well as the tumour microenvironment, by reversible modulation of

cell adhesion, onset of signalling pathways and acquisition of novel migratory and

invasive capacities. The Metafi ght consortium is strengthened by established

combined expertise on adhesion receptor signalling and the availability of unique

tumour cell and cancer animal model systems. The project will characterise known

and novel components of the Core Invasive Machinery responsible for development

and homing of metastasis, by innovative in vivo non-invasive imaging techniques.

The Metafi ght project comprises seven major interrelated Work Packages (WP). WP1

is designed to investigate the molecular and functional architecture of the Core

Invasive Machinery, on which tumour cell migration and eventually invasion depend.

WP2 and WP3 will screen for key modulators of metastasis formation in in vivo

murine models by non-invasive imaging techniques. WP4 is related to a

comprehensive proteomic analysis of expression and phosphorylation of the

candidate modulators in metastasis formation. WPs1-4 feed into WP5, which builds

upon and exploits knowledge generated in the fi rst four and translates it into

existing pharmacological interventions to generate new candidate drugs. This will

lead to patent fi ling and licensing strategies. WP6 and WP7 will handle dissemination

and management activities. The outcomes will include improvement of health and

reduction of health expenses, as well as the creation of new jobs and economic

benefi t.

Coordinator Dr Paola Defi lippiUniversità degli Studi di Torino, Turin, Italy

e-mail paola.defi [email protected]



Duration 36 months

Project website http://www.metafi ght.eu/


METOXIA

Metastatic tumours facilitated by hypoxic Tumour Micro-Environments

Recent research suggests that the hypoxic micro-environment of tumours is one of

the major drivers of the metastatic spread of cancer. Moreover hypoxic tumour

micro-environments may result in treatment resistance of cancer cells, therefore

causing a double eff ect of reducing the potential for successful treatment of the

patient. This project seeks to clarify the roles and functions of the hypoxic tumour

micro-environment in relation to the survival of solid tumours that are likely to

metastasise. METOXIA will gain new knowledge about the molecular mechanisms

underlying hypoxia-driven metastasis, such as the epithelial-mesenchymal

transition (EMT), by several routes: (a) mechanisms related to cell growth and cell

proliferation (UPR, mTOR, CA9, HIF, Notch, and VHL); (b) angiogenesis and

lymphangiogenesis; (c) metabolism and pH-regulation; and (d) the handling of

reactive oxygen species (ROS). It will generate animal models for the study of the

role of hypoxia in metastases and develop a bio-bank of tumour and blood samples

for molecular diagnostic studies. The project will identify and develop advanced

imaging techniques and biomarkers and identify micro-metastases in the bone

marrow of patients, in order to assist in the selection of appropriate stratifi cation of

the actual primary tumours’ and metastases’ micro-environmental conditions. It will

also create a machine-learning-based classifi er of tumour hypoxia. The consortium

has the necessary expertise to undertake proof-of-principle clinical tests of new

treatment strategies, and will accordingly perform clinical tests of new drugs

developed to attack the regulatory mechanisms selected from the pre-clinical work,

as well as possible synergisms of combined treatments. METOXIA will also test new

radiotherapy strategies for treatment of primary as well as metastatic tumours.

Cancer types chosen for clinical studies are non-small-cell lung carcinoma, squamous

cell carcinoma of the larynx, prostate cancer, primary breast cancer and rectal cancer.

Coordinator Dr Erik PettersenUniversity of Oslo, Oslo, Norway




Duration 60 months

Project website http://www.uniforum.uio.no/nyheter/2008/05/samlar-europeiske-forskarkrefter-mot-kreften.html

26

MICROENVIMET

Understanding and Fighting Metastasis by Modulating the Tumour Microenvironment through Interference with the Protease Network

The MICROENVIMET project proposes innovative approaches to building a

comprehensive understanding of the interplay between cancer cells and their

microenvironment at both primary and secondary sites. The objectives are to

identify molecular pathways involved in the regulation of metastatic dissemination

to lung, liver, lymph node and bone. To achieve these objectives, the original

experimental approach proposed is to modulate the production/activity of proteases

or their inhibitors. Proteases are now recognised as key regulators of a complex

network of interacting molecules that modulate the properties of cancer cells and

their microenvironment. The project plans to identify key molecular pathways

underlying early steps of metastatic dissemination, by interfering with the protease

network and studying the impact of such experimentally manipulated

microenvironments on metastasis formation. In addition to identifying key

regulators of metastasis, it aims to develop blocking antibodies in respect of these

new candidates, with effi cacy for therapeutic intervention using the most advanced

state-of-the-art technologies. The study of cancer stem cells will be integrated into

current concepts that consider and attempt to explain the importance of the

microenvironment during cancer progression. The consortium will facilitate shared

access to a new microRNA platform, to innovative technologies, human tumour

tissue banks, in vivo and in vitro models mimicking diff erent steps of metastatic

dissemination, as well as know-how in tumour-host cell interplay, angiogenesis,

lymphangiogenesis, cancer stem cell biology, and generation of a database.

Coordinator Dr Agnes NoëlUniversité de Liège, Liège, Belgium




Duration 48 months

Project website http://www.microenvimet.eu/


MISMATCH2MODEL

Characterisation and quantitative Modelling of DNA mismatch Repair and its Role in the Maintenance of genomic Stability and Cancer Avoidance

DNA mismatch repair (MMR) plays a crucial role in the maintenance of genomic

stability. In both bacteria and eukaryotes, the loss of mismatch repair gives rise to a

mutator phenotype. In hereditary non-polyposis colon cancer (HNPCC) families,

germ-line mutations in one MSH2, MSH6 or MLH1 allele predispose to cancer of the

colon, endometrium, ovary and other organs. HNPCC is the most frequent form of

familiar cancer. The MISMATCH2MODEL project will adopt and exploit a systems

biology approach, combining European expertise in DNA mismatch repair with

sophisticated multidisciplinary technology and expertise in quantitative modelling,

in order to describe this DNA repair process at diff erent levels of complexity. The

multidisciplinary consortium will have the following tasks that relate directly to the

topics raised in Call HEALTH 2.1.2.5: (a) gather quantitative and structural data sets

describing the principal steps of DNA mismatch repair; (b) integrate and analyse

structural and functional data obtained from single molecule and bulk studies; (c)

develop mathematical models for single and/or multiple steps of the MMR pathway;

(d) perform analyses at diff erent levels of complexity, from recognition of the

mismatch through repairosome assembly to in vivo function; and (e) combine the

well-understood MMR E.coli model system with the cancer-protective human

system. The combination of the individual strengths of the multidisciplinary groups

involved in this programme ensures that signifi cant progress will be made towards

the understanding of this complex process.

Coordinator Dr Rini De Crom Erasmus Universitair Medisch Centrum Rotterdam, Rotterdam, The Netherlands



Duration 48 months

Project website http://cordis.europa.eu/fetch?CALLER=FP7_PROJ_EN&ACTION=D&DOC=1&CAT=PROJ&RCN=88358

28

NANOPHOTO

Targeted Nanosystems for Improving Photodynamic Therapy and Diagnosis of Cancer

The overall objective of this proposal is the development of one or more nanosystems

loaded with Foscan® and conjugated to cancer-cell-specifi c ligands to improve the

effi cacy and selectivity of photodynamic therapy (PDT) and optimise a fl uorescence-

based tumour imaging approach. At present, PDT with Foscan® can be very eff ective

but non-selective as the Foscan® accumulates in tumour tissues as well as healthy

ones. Any major improvement of the therapy will only come with the availability of

a carrier capable of seeking out cancer cells and delivering Foscan® selectively to

them. Three types of nanosystems – liposomes, silica nanoparticles and poly(lactide-

co-glycolide) copolymer nanoparticles – have been selected as potential nanocarriers

for the selective delivery of Foscan®. The selection is based mainly on the diff erent

chemical nature of these systems which can aff ect biocompatibility. During the fi rst

part of the project each type of nanosystem will be optimised through in vitro and in vivo tests, and leader nanocarriers will be selected and conjugated to cancer cells’

specifi c ligands to increase the selective delivery of Foscan®. The ligands used (folic

acid, EGF and antibodies) to target the nanosystems fi nd their corresponding

receptor over-expressed on the surface of cancer cells, thereby permitting a selective

delivery of drugs to these cells. In vitro and in vivo investigations will be carried out

to demonstrate the validity of our approach and deliver, at project conclusion, a fi nal

product which can then be tested clinically. Because of the red fl uorescence emitted

by Foscan®, once it has selectively accumulated in cancer cells, a fl uorescence-based

technique can be used for tumour imaging and diagnosis. The project therefore

expects to develop a Foscan®-loaded nanosystem(s) which can be used for

improving both therapeutic and tumour imaging approaches.

Coordinator Dr Elena ReddiUniversita' degli Studi di Padova, Padova, Italy




Duration 36 months



ONCOMIRS

MicroRNAs and Cancer: From Bench to Bedside

Although studies addressing their role in cancer pathogenesis are at an early stage,

it is apparent that specifi c microRNAs (miRs) and molecules involved in their

biogenesis contribute to tumorigenesis. First, this project will identify and expose

novel miRs and components of their biogenesis machinery, and investigate links

between these molecules and human cancers. Secondly, it will connect the

information obtained on deregulated miRs with known cellular pathways involved in

cancer, such as the p53 tumour suppressor pathway. To establish a causal relationship

between dysregulated miRs and cancer development, the project will then model

the tumorigenic processes in mice lacking or overexpressing particular miRs. Finally,

since the specifi city and potency of some miRs suggest that they might be promising

as therapeutic agents, these models will be used in conjunction with other cancer

models to explore miR-based therapeutic strategies.

Coordinator Dr Jean-Christophe MarineFlanders Interuniversity Institute for Biotechnology, Gent, Belgium




Duration 60 months

Project website http://www.dmbr.ugent.be/oncomirs/index.html

30

OPCARE9

A European Collaboration to optimise Research for the Care of Cancer Patients in the last Days of Life

The project aims to explore, share and collate existing knowledge and practice

relating to each of the key themes identifi ed within the work programme. It aims to

reach consensus – based on current practice and available research evidence – on

the optimum care to be delivered in the last days of life and on the gaps in the

knowledge base. In addition, it aims to develop innovative ways of addressing these

gaps with the specifi c aim of improving care for cancer patients in these last days of

life. Clearly, such improvements will also impact positively on their informal carers

and those health professionals delivering the care. Importantly, it aims to do this

systematically and collaboratively across Europe and beyond, in order to integrate

knowledge from a range of healthcare environments and cultures, and to avoid

duplication of resources and eff ort.

Coordinator Dr John EllershawThe University of Liverpool, Liverpool, UK




Duration 36 months

Project website http://www.liv.ac.uk/mcpcil/research-development/opcare9.htm


O-PTM-BIOMARKERS

Discovery of novel Cancer Serum Biomarkers based on aberrant Post-Translational Modifications of O-glycoproteins (O-PTM-Biomarkers) and their application to early detection of cancer

Early detection accomplished through an effi cient screening programme remains

the most promising approach to improving the long-term survival rate of cancer

patients. There is a pressing need for the development of biomarkers which detect

the early changes in those cases where the clinical symptoms appear only after the

cancer has progressed and treatment is no longer eff ective. This proposal, which

addresses the problem at the European level, combines two unique features: 1) large

and unique collections of sera with the potential for evaluation of diagnostic serum

biomarkers with high statistical power, and 2) a novel technological approach

involving specifi c immunodetection of cancer-associated Post-Translationally

Modifi ed (PTM) glycoproteins in serum and of the auto-antibodies to these

glycoproteins. Glycosylation of proteins is one of the most abundant and complex

forms of post-translation modifi cations and the most important for the cell surface

and secreted proteomes. O-glycosylation (O-PTM) is always altered in carcinomas,

creating novel O-PTM epitopes which induce auto-antibodies. The main objectives

are therefore to: 1) use a novel glycopeptide microarray technology to identify,

evaluate and validate an O-PTM auto-antibody signature as an early diagnostic

biomarker, focusing on breast, ovarian, pancreatic and lung cancers; and 2) develop

and validate novel ELISA-type assays for cancer-specifi c glycoforms of the MUC1 and

MUC16 glycoproteins (targets of current serum biomarker assays). The project brings

together a consortium of participants from fi ve Member States to exploit the

potential of the unique serum banks at a European level by, fi rst, integrating the

expertise of world leaders in glycobiology with cancer physicians and experts in

biomarker assays and, second, establishing a functional interaction between

academic groups and commercial enterprises committed to improving cancer

therapy and diagnosis.

Coordinator Dr Joy BurchellKing's College London, London, UK




Duration 36 months


32

PRISMA

Reflecting the Positive diveRsities of European prIorities for reSearch and Measurement in end of life cAre

There is little coordination in undertaking research in end-of-life care. This is due to

lack of agreement on what constitutes ‘end of life’ cancer care, no information on

public or clinical priorities for achieving a ‘good death’ in a culturally diverse Europe,

few appropriate measures of quality, and a lack of established best practice. PRISMA

aims to deliver an integrated programme to coordinate research priorities and

practice. The work packages will undertake actions to identify cultural diff erences in

end-of-life care, establish a collaborative research agenda informed by public and

clinical priorities, and draw together best practice and resources for quality

measurement. The Palliative Outcome Scale (POS) is a multidimensional tool that

measures the physical, psychological, spiritual and information needs of patients

and families at the end of life. It has been culturally adapted to 20 EU countries and

widely used by over 100 services to evaluate and improve quality of care. However,

there have been no opportunities to share practice, identify shared and country-

specifi c domains, and collaborate in improving research across Europe. By

coordinating POS use, PRISMA off ers a model to optimise end-of-life care research

and measurement, and to identify both commonalities and diff erences in the

evaluation of quality indicators for cancer patients and their families across Europe.

Incorporating wide public/clinical consultation with the coordination of POS use will

advance scientifi cally sound practice while taking account of cultural diff erence and

public expectations. Through integrated action, the project will exchange experience,

shape best practice, and plan future collaboration through identifi cation of priorities.

This will enable research to harmonise and refl ect the diversity and the needs of

Europe’s citizens and clinicians. Support for the Palliative Outcome Scale will ensure

a direct impact between research and daily clinical practice.

Coordinator Dr Richard HardingKing’s College London, London, UK




Duration 36 months

Project website http://www.kcl.ac.uk/schools/medicine/depts/palliative/arp/prisma/


PROACTIVE

High-throughput Proteomics Systems for accelerated Profiling of putative Plasma Biomarkers

The PROACTIVE consortium aims to develop the multiplexed proximity ligation assay

into a high-throughput protein detection and quantifi cation technology supported

by novel data management and analysis tools. Hundreds of putative biomarkers of

the plasma proteome can then be assayed with high sensitivity in minute sample

volumes, far surpassing any current capabilities. The consortium combines three

European SMEs with synergistic competences in technology development, reagent

manufacturing, and software development for data management and analysis.

Together with clinical cancer scientists, biostatisticians and the diagnostics industry,

these high-capacity tools will be evaluated in pilot projects for cancer biomarkers

using biobanked samples. Preliminary data in the literature attest to improved

diagnostics with the use of multiple complementary protein markers. However,

there is a lack of suitable high-throughput procedures for identifying new markers

and determining which markers complement each other in eff ective diagnostic

panels. Better capabilities in diagnosing cancer at the early and most curable stages

will greatly improve human health and reduce healthcare costs. Patient stratifi cation

is also in need of better diagnostics to facilitate the selection of appropriate patient

care. Many clinically used immunoassays capable of diagnosing cancer have been in

use for many years as single markers, but with limited sensitivity and specifi city. No

marker can today single-handedly diagnose all cases with the desired accuracy for a

specifi c cancer type, also the performance of these markers is limited in the earliest

stages of the disease. At the conclusion of this collaborative project, the research and

innovation achieved by the consortium will enable the partners to position

themselves at the forefront of high-throughput biomarker research, strengthening

their competitiveness in the international arena.

Coordinator Dr Simon FredrikssonOLINK AB, Uppsala, Sweden




Duration 36 months

Project website http://www.olink.se/proactive/proactive_content.php

34

PROMARK

Genetic Prostate Cancer Variants as Biomarkers of Disease Progression

Prostate cancer is the most common cancer in males in Europe, causing over 87 000

deaths in 2006. Early diagnosis and treatment are key factors in determining

survival, but screening methods based on the commonly used PSA blood test have

low specifi city and result in excessive treatment of localised lesions that might never

progress to symptomatic cancer. Biomarkers that help determine which of the early-

stage tumours will remain confi ned to the prostate and which will progress to an

invasive, aggressive form of the disease are urgently needed. Using genome-wide

association analysis, the consortium has identifi ed four distinct common genetic

variants that increase the risk of prostate cancer, some of which may have a stronger

association with severe disease. Furthermore, by comparing the genotypes of

patients with aggressive disease to genotypes of those with a more indolent form,

the team has identifi ed a large number of candidate markers of disease severity.

Here, the project plans to take all these inherited variants and test the hypothesis

that they can serve as biomarkers for prostate cancer prognosis and outcome, as

well as select two of these variants for genomic and functional studies. Specifi cally,

the project will: 1. collect DNA and clinical data from over 8 000 prostate cancer cases

in four European populations (Iceland, the Netherlands, Romania and the UK); 2. test

the utility of inherited prostate cancer risk variants as biomarkers of disease severity,

progression and outcome; and 3. start dissecting the biological mechanisms that

cause increased prostate cancer risk The expected outcomes of the project are: a) a

new prognostic test that predicts clinical outcomes for localised prostate cancer

more accurately than existing methods: b) documentation of the association of

genetic risk variants with clinical parameters and outcomes; and c) an enhanced

understanding of carcinogenesis of the prostate which may lead to the identifi cation

of additional biomarkers or therapeutic targets.

Coordinator Dr Thorunn Rafnardecode Genetics, Reykjavik, Iceland




Duration 60 months

Project website www.promark-fp7.eu


PROSPER

Prostate Cancer: Profiling and Evaluation of ncRNA

Annually, over 200 000 new prostate cancer cases are diagnosed in Europe. This

number is expected to increase due to the widespread introduction of prostate

specifi c antigen (PSA) tests on asymptomatic men and an ageing population,

leading to a high rate of over-detection with most cases never experiencing cancer

symptoms during their lifetime. This current lack of accurate prostate cancer

prognosis will have a devastating impact on both life quality and healthcare

expenditures. Molecular mechanisms in the development of prostate cancer are

largely unknown, apart from the recognised role of androgens, and this lack of

knowledge hampers the development of effi cient prevention, specifi c diagnostics,

and prognostic and therapeutic tools. The project’s planned studies of ncRNAs can

contribute major breakthroughs, optimising individualised prostate cancer treatment

by providing both novel biomarkers and drug targets. The project will pursue two

major clinical problems: 1) early identifi cation of cases requiring aggressive curative

treatment, and 2) the development of effi cient therapies for hormone-refractory

prostate cancer. The project will cover all phases of translational research, from

discovery to validation and implementation, will identify novel ncRNAs, investigate

their expression, genetic/epigenetic alterations and function, and will develop

diagnostic tools, and identify and validate therapeutic targets.

Coordinator Dr Tapio VisakorpiTampereen Yliopisto, Tampere, Finland




Duration 48 months

Project website http://www.uta.fi /imt/ProspeR/

36

SFMET

HGF/SF and MET in Metastasis

The growth and motility factor HGF/SF and its receptor MET defi ne a paracrine

signalling system which controls the migration of several cell lineages in

embryogenesis and tissue repair. In a large number of human tumours, cancer cells

‘hijack’ HGF/SF and MET signalling in order to invade adjacent tissue and initiate

metastasis. The evidence for this is strong, broad and consistent, and highlights HGF/

SF and MET as key eff ectors of tumour invasion and primary targets for therapy. This

proposal has two objectives. The fi rst is to understand the mechanism by which HGF/

SF and MET cause tumour invasion, and specifi cally how local hypoxia induces MET

over-expression in tumour cells and how the MET-WNT and the MET-chemokine

pathways cooperate in metastasis. The second aim is to develop MET therapeutics,

including (i) a protein antagonist built from a fragment of the ligand known as NK1,

(ii) low molecular weight MET antagonists, and (iii) inhibitors of SHP-2, a critical

eff ector of MET signalling. NK1 will be engineered as a receptor antagonist on the

strength of the available crystal structures. Low molecular weight MET antagonists

and SHP-2 inhibitors will be developed on the strength of the availability of

recombinant forms of the target proteins, suitable screening methodologies, and the

results of initial screens that have provided robust proof of principle for both

approaches. The project builds on the strong progress in the participating

laboratories into the structure and function of HGF/SF and MET and fulfi ls the three

key criteria described in the Call for Proposals ‘Understanding and fi ghting

metastasis’, namely (i) it addresses a key mechanism of dissemination of human

tumours, (ii) it contributes to understanding the interplay between the tumour

microenvironment (the source of HGF/SF) and tumour cells (the cells that express the

MET receptor), and (iii) it off ers considerable prospects of delivering novel

therapeutics for metastatic cancer.

Coordinator Dr Ermanno GherardiThe Chancellor, Masters and Scholars of the Universityof Cambridge, Cambridge, UK




Duration 36 months

Project website http://www2.mrc-lmb.cam.ac.uk/sfmet/index.html


SKINSPECTION

Multimodal Skin Inspection with hybrid acoustic and optical Spectroscopic Imaging

The incidence of skin cancer in Europe, the US and Australia is rising rapidly. One in

fi ve will develop some form of skin cancer during lifetime. A person has a 1:33 chance

of developing melanoma, the most aggressive skin cancer. Melanoma is the second

most common cancer in women aged 20-29, and the sixth most common cancer in

men and women. In 2007, more than one million new cases will be diagnosed in the

US alone. About 90% of skin cancers are caused by ultraviolet (UV) sunlight. The

World Health Organization estimates that 60 000 people will die this year from too

much sun: 48 000 from melanoma and 12 000 from other types of skin cancer.

A signifi cant improvement in the current diagnostic tools of dermatologists is required

in order to identify dermal disorders at a very early stage, as well as monitor directly

the eff ects of treatment. This project proposes the development of a non-invasive

multimodal hybrid imaging system with the capability to perform non-invasive

high-resolution three-dimensional clinical (i) two-photon imaging with time-

correlated single photon detection, (ii) autofl uorescence lifetime imaging, (iii) high-

frequency acoustical imaging with novel miniaturized multiple detector arrays, and

(iv) optoacoustical imaging using ultrashort near-infrared (NIR) laser pulses. This

novel multimodal approach will provide a wide-fi eld acoustic/optoacoustic view

with quantitative depth information of the dermatological lesion, as well as a close

‘optical’ look into particular intratissue compartments with quantitative hyper-

spectral information and subcellular resolution. A successful outcome will provide

a unique tool for early diagnosis and treatment control of skin cancer and skin

disease, and will signifi cantly contribute to the improvement of the European

healthcare system.

Coordinator Dr Robert LemorFraunhofer-Gesellschaft zur Förderung der Angewandten Forschung e.V, Sankt Ingbert, Germany




Duration 48 months

Project website http://www.skinspection-fp7.eu/

38

TARCC

Targeting Alpha-particle emitting Radionuclides to Combat Cancer

This project aims at improving drug delivery to cancer cells by developing targeted

radiotherapy with alpha-emitting radionuclides. Alpha particles emitted by

radionuclides have short tracks (about 100 microns) in body tissues and, as a result,

are likely to be most appropriate in treating small-size tumours and isolated cancer

cells. This project proposes the development of improved vectors and targeting

technology based on specifi c targeting agents (recombinant antibody fragments

and synthetic peptides), pretargeting approaches and nano-colloids specifi cally

designed to deliver alpha-emitting radionuclides to cancer cells after local or

systemic administration. The concept of an in situ generator permitting the use of

longer half-life parents of alpha-emitting radionuclides will also be developed.

Several approaches to preventing the release of radionuclides after parent isotope

disintegration, including encapsulation in nano-colloids, are proposed. Improved

targeting methods will be tested in animal models of small-size tumours and

associated dosimetry (including micro-dosimetry) and toxicity studies will be

performed. The fi nal goal of the project will be to propose one or several new

products for targeted delivery of alpha-emitting radionuclides for clinical

development.

Coordinator Dr Jacques BarbetNational Institute of Health and Medical Research– Institut National de la Santé et de la Recherche Médicale (INSERM), Nantes, France




Duration 36 months

Project website http://tarcc.org/


TELOMARKER

Identification and Characterisation of novel Human Telomere-related Biomarkers that aid cancer management by improving patient diagnosis, treatment selection, response monitoring and drug development

Telomeres are DNA-nucleoprotein structures that protect the ends of human

chromosomes through the formation of a ‘cap’ that prevents exonucleolytic

degradation, inter- and intra-chromosomal fusion and subsequent chromosomal

instability. Telomerase, the ribonucleoprotein enzyme that maintains linear

chromosomal DNA ends, by the addition of TTAGGG repeats, is completely repressed

or present only at low, tightly regulated levels in normal human cells as a safeguard

against cancer. Normally, telomere shortening in the absence of suffi cient telomerase

leads to telomere uncapping, activation of a DNA damage response, and either

replicative senescence or apoptosis. As a result, telomeres become dysfunctional in

human cancers. Individual protein components of the core telomere higher-order

structure, known as the telosome or shelterin complex, represent highly promising

candidates for novel biomarkers of telomere dysfunction and human cancer

progression. TeloMarker will identify, characterise and validate novel telomere-

related biomarkers. Biomarker discovery will be based both on known telosomal

components and newly discovered affi liated proteins, as well as on telomerase and

its recruitment factors. Novel telomere-related cancer biomarkers promise to

improve radically early diagnosis, patient treatment selection, prognostic evaluation

and outcome monitoring, as well as furnish new molecular targets for the

development of novel small-molecule anti-cancer drugs.

Coordinator Dr Robert NewboldBrunel University, Uxbridge, UK




Duration 36 months

Project website www.brunel.ac.uk/research/TeloMarker

40

TuMIC

An integrated Concept of Tumour Metastasis: Implications for Therapy

From many perspectives the concept of the process of metastasis is inadequate and

needs to be revised. In particular, recent ideas about the cellular basis of tumour

growth (cancer stem cells) and the establishment by remote tumours of special

permissive microenvironments in target organs prior to metastasis (metastatic

niches) remain to be explored. The TuMIC project will use novel experimental

approaches to integrate these newly emerging principles and ideas with the

diff erent hypotheses that have until now tried to explain the process of metastasis.

Specifi cally the project aims to understand how cancer stem cells behave in and

contribute to metastasis, and how networks and pathways that are known to

regulate metastasis aff ect their properties. Further objectives are to determine how

a permissive microenvironment for metastasis formation is established in given

organs, how this contributes to determining patterns of metatasis, and how these

microenvironments interact with cancer stem cells. These studies will facilitate the

development of an improved and more accurate concept of the process of metastasis.

In turn, this will have fundamental ramifi cations for the way novel anti-cancer

therapies are designed and, most importantly, should provide important new

insights into how cancer and in particular metastatic disease can be successfully

treated. With this in mind the project will also perform preclinical studies that build

on TuMIC fi ndings, with the aim of developing novel anti-cancer therapies.

Coordinator Dr Jonathan SleemanRuprecht-Karls-Universität Heidelberg, Mannheim, Germany




Duration 48 months

Project website http://itgmv1.fzk.de/www/tumic/tumic_main.htm


UROMOL

Prediction of Bladder Cancer Disease Course using Risk Scores that combine molecular and clinical Risk Factors

Bladder cancer is a recurrent and very prevalent cancer which generates the highest

cost per patient in Europe. New genomic methods have allowed the identifi cation of

novel markers with potential clinical application. However, due to the use of single-

marker assays and poor study design, none of these markers has made it to the

clinic. FGFR3 and PIK3CA mutations, expression profi les, and microsatellite alterations

in tumour tissue and urine, as well as polymorphisms in immune response genes,

are very promising biomarkers that predict the presence of a tumour in the bladder,

and the likelihood of progression and invasion of the muscle. The project proposes to

combine the best markers of bladder cancer outcome in a prospective multi-centre

validation study in Spain, the Netherlands, Sweden and Denmark as genetic

predictors. The approach is a pre-defi ned, standard operating procedure-based

prospective study with fi xed end-points, testing relatively few independent

variables in tumour tissue, urine and blood. To obtain a seamless introduction into

the clinic, the project will use a mathematical approach in which the best markers

are weighted based on disease models and nomogram construction, leading to a

risk score applied to each patient at each visit. The validated biomarkers will lead to

specifi c recommendations for changes in patient management based on the risk

scores. A saving of more than euro 40 million is estimated annually, based on a

reduced frequency of cystoscopies, as well as an increased survival and a better

quality of life for the patients.

Coordinator Dr Torben ØrntoftAarhus Universitetshospital, Skejby, Aarhus, Denmark




Duration 60 months

Project website http://uromol.eu/index.php?option=com_content&task=view&id=14&Itemid=27

42

ZF-CANCER

Developing high-throughput Bioassays for Human Cancers in Zebrafish

Recently the zebrafi sh has emerged as a new important system for cancer research,

as its genome contains all the orthologs of human oncogenes and forms tumours

with similar histopathological and gene profi ling features as human tumours. The

zebrafi sh thus provides an in vivo vertebrate model for identifying novel mechanisms

of cancer progression and for the development of new anticancer compounds in a

time- and cost-eff ective manner. The ZF-CANCER project aims to develop high-

throughput bioassays for target discovery and rapid drug screenings applicable in

preclinical validation pipelines. Fluorescently labelled human and zebrafi sh cancer

cells will be implanted (xenogenic and allogenic transplantation) in zebrafi sh

embryos transgenic for a GFP-vascular marker, and quantitative, multi-colour

fl uorescent intravital bio-imaging of tumour progression will provide the readout.

Because of its amenability to genetic manipulation and optical transparency, the

zebrafi sh is currently the only vertebrate model that allows the simultaneous in vivo imaging of all hallmarks of cancer progression including cell survival, proliferation,

migration and induction of angiogenesis. The combination of visual, non- invasive

monitoring in translucent host embryos with powerful RNA interference technology,

successfully developed for human cancer cells, will enable identifi cation of novel

targets in a wide variety of human cancers. Automation of these fl uorescent

readouts will accelerate the screening process with chemical libraries and will help

identify new compounds involved in diff erent aspects of cancer progression and

inhibition. In the case study, a selected panel of genes and lead compounds will be

screened on a high-throughput platform, possibly resulting in the identifi cation of

important anti-tumour drugs relevant for human cancer therapy. Fundamental

knowledge, tools and technical expertise gained from ZF-CANCER will be

commercially exploited by a company and two high-tech SMEs.

Coordinator Dr Ewa Snaar-JagalskaUniversiteit Leiden, Leiden, The Netherlands




Duration 36 months

Project website http://biology.leidenuniv.nl/ibl/S1/research/ZF-CANCER/


European Commission

EUR 24042 EN – Cancer research – EU Funding (2007-2009)

Luxembourg: Office for Official Publications of the European Communities

2009 – 44 pp. – 10.5 x 21 cm

ISBN 978-92-79-12358-0

ISSN 1018-5593

DOI 10.2777/20858

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It is available in English, French, German and Spanish.

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Area: Cancer

Contact: Jan-Willem van de Loo, PhD


European Commission

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B–1049 Brussels

This booklet gives a short overview of cancer research projects that have been funded sofar under the European Union’s Seventh Framework Programme (FP7; 2007-2013) – the EU’s main instruments for funding research in Europe.

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Cancer research EU Funding (2007-2009)

Documents

KI-NA-24-042-EN-C Cancer research