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• the identifi cation and molecular/functional characterisation<br />
of natural mechanisms of telomerase<br />
repression and cell self-renewal (including hTERT<br />
repressor genes and chromatin remodelling factors)<br />
in normal human cells and their dysregulation in<br />
human cancers;<br />
• understanding the mechanisms of action and pharmacological<br />
activity of existing small molecule telomerase<br />
inhibitors (eg BIBR1532);<br />
• establishment of the precise roles of telomere aggregates<br />
and telomere-length-independent functions of<br />
telomerase in human cancer.<br />
• An advanced molecular understanding of telomerase<br />
regulation at chromosome ends (eg involving the key<br />
telomere-binding proteins POT1 and hEST1A) and a comprehensive<br />
evaluation of such proteins as anti-telomerase<br />
drug targets.<br />
• New and eff ective molecular inhibitors (eg siRNAs,<br />
ribozymes and peptide nucleic acids) of telomerase and<br />
telomere maintenance (targeting hTERT transcription<br />
and telomere-related proteins discovered within the MOL<br />
CANCER MED consortium) for the purpose of vasli.<br />
• Panels of new molecular markers of telomerase repression,<br />
telomere maintenance and associated signalling<br />
pathways, that can be developed into precise, rapid<br />
assays for use in novel ‘kits’ for early cancer diagnosis and<br />
prognostic evaluation.<br />
• An understanding of the diff erential eff ects of telomerase/telomere<br />
maintenance inhibition on normal human<br />
tissues and in cancers using organotypic in vitro human<br />
cell models.<br />
• Rational design of libraries of novel small molecule compounds<br />
for screening against new targets, and selection<br />
of small molecule antitelomerase/telomere maintenance<br />
drug leads active against individual new targets discovered<br />
during the course of MOL CANCER MED.<br />
• Identifi cation of potential anti-cancer drugs from the<br />
above, following biochemical, pharmacological and functional<br />
(in vitro and in vivo) anti-tumour assays.<br />
• Preclinical exploitation of potential novel cancer drugs<br />
through interface with clinical oncology centres and SMEs.<br />
Potential applications<br />
The emphasis of the LIFESCIHEALTH Priority is very fi rmly<br />
placed upon multidisciplinary translational research, in which<br />
fundamental scientifi c knowledge is harnessed for the specifi<br />
c purpose of generating, within the timeframe of FP6,<br />
reagents, treatments and diagnostics that are of clinical value.<br />
In MOL CANCER MED, a highly focused strategy will be<br />
adopted towards applying molecular genetic knowledge<br />
about the mechanisms underlying the cancer process to<br />
the development of completely new approaches to cancer<br />
treatment, eg in bringing molecular biology, cell biology,<br />
genomics and target evaluation together with small molecule<br />
drug discovery.<br />
54<br />
Coordinator<br />
Robert Newbold<br />
Brunel University<br />
Uxbridge, United Kingdom<br />
robert.newbold@brunel.ac.uk<br />
Partners<br />
Stephen Neidle<br />
London School of Pharmacy<br />
London, United Kingdom<br />
Jean-Louis Mergny<br />
INSERM<br />
Paris, France<br />
John Mann<br />
Queens University Belfast<br />
Belfast, United Kingdom<br />
Maurizio D’Incalci<br />
Istituto de Richerche Mario Negri<br />
Milan, Italy<br />
Joachim Lingner<br />
EPFL<br />
Lausanne, Switzerland<br />
Kenneth Parkinson<br />
QMUL<br />
London, United Kingdom<br />
Project number<br />
LSHC-CT-2004-502943<br />
EC contribution<br />
€ 4 000 000<br />
Duration<br />
48 months<br />
Starting date<br />
01/10/2004<br />
Instrument<br />
IP<br />
Project website<br />
www.brunel.ac.uk/<br />
research/molcancermed/<br />
Uwe Martens<br />
Medical University Center Freiburg<br />
Freiburg, Germany<br />
Petra Boukamp<br />
DKFZ<br />
Heidelberg, Germany<br />
Maria Blasco<br />
CNIO<br />
Madrid, Spain<br />
Keith Nicol<br />
University of Glasgow<br />
Glasgow, United Kingdom<br />
Nadia Zaffaroni<br />
National <strong>Cancer</strong> Institute<br />
Milan, Italy<br />
Nedime Serakinci<br />
University of Southern Denmark<br />
Vejle, Denmark<br />
Goran Roos<br />
Umeå University<br />
Umeå, Sweden<br />
CANCER RESEARCH PROJECTS FUNDED UNDER THE SIXTH FRAMEWORK PROGRAMME
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