Cancer Research - Europa

Keywords | Angiogenesis | vasculogenesis | blood vessels | tumour | endothelial cells | clinical trials |
microarrays | proteomics molecular targets |
ANGIOTARGETING
Multidisciplinary research to explore
and validate molecular targets
for innovative treatments
Summary
Solid tumour growth depends on the recruitment of new
blood vessels that will provide the cancer cells with nutrients
and oxygen. The ANGIOTARGETING project intends to
fi nd new targets on the tumour vasculature. The project will
then defi ne these targets and develop new therapeutic
strategies towards them.
The apparent limited success in translating angiogenesis
research into the clinic is, in our view, based on the fact that
the research fi eld has been fragmented, and no standardised
tools and models have been identifi ed that reliably
refl ect the complexity of tumour angiogenesis mechanisms
in humans.
ANGIOTARGETING will identify and validate new therapeutic
targets directed towards tumour vascular-matrix
interactions, develop new therapeutic strategies and implement
such strategies in pre- and clinical trials. The project
represents a virtual research institute in Europe and consists
of 14 highly competent research centres within the
fi eld of angiogenesis research. To defi ne and validate new
targets related to the tumour vascular transcriptome and
proteome, the consortium will establish high throughput
functional screening technologies for the identifi cation of
novel secreted factors that regulate endothelial cell growth
and survival. This includes the use of robotic platforms that
will be used to identify cDNAs with specifi c cellular functions.
In this project, basic science, translational research
and clinical activities are strongly integrated, in order to
validate defi ned targets and to develop new therapeutic
principles for clinical implementation.
Problem
The signifi cant role of neovessel formation in health and disease
has been clearly demonstrated during the last decade.
The molecular mechanisms that lead to the establishment of
functional blood vessels are also key factors that regulate
tumour progression. Considerable eff orts have been devoted
to research identifying the mechanisms that regulate the
recruitment of blood vessels to tumours. Under normal
conditions, the establishment of blood vessels is a highly
complex and coordinated biological process.
Targeting non-cancer cells that feed and drain the tumour and
form channels through which tumour cells can disseminate,
rather than targeting the neoplastic cells themselves, represents
an approach to cancer therapy that holds particular
promise because these cells are genetically stable, and therefore
less likely to accumulate mutations that allow them to
develop drug resistance. The fi rst meaningful clinical eff ects
of antiangiogenic therapy in human cancer have recently been
demonstrated. However, in spite of some highly encouraging
results, most angiogenesis inhibitors, reported to suppress
tumour growth in animal models, have thus far failed in human
clinical trials. In our view, this refl ects that no standardised
tools and models have been identifi ed that reliably refl ect the
complexity of tumour angiogenesis mechanisms in humans.
The successful translation of potential angiogenesis inhibitors
to clinical application depends partly on the transfer of expertise
from scientists who are familiar with the biology of
angiogenesis to clinicians, as well as an active feedback from
the clinicians to the scientists.
ANGIOTARGETING aims at the identifi cation and validation
of new therapeutic targets in tumour vasculature, develops
new therapeutic strategies and implement such strategies
in pre- and clinical trials. A strong focus on translational
research and clinical implementation will convert R&D results
into direct public and economic benefi ts.
BIOLOGY 13
Aim
The objective is the identifi cation and validation of new
therapeutic targets directed towards tumour vascularmatrix
interactions.
Expected results
• The project will increase our understanding of how
tumours generate a vascular supply.
• The project will develop new technologies to defi ne
and validate key molecular targets that control tumour
vascularisation and invasion.
• The project will identify potential therapeutic targets
towards the tumour vascular and invasive transcriptome
and proteome.
• The project will develop comprehensive bioinformatics
tools for the analysis of high throughput gene and protein
data from defi ned cell populations within tumours.
• The project will develop state-of-the-art platforms for
preclinical and clinical assessment of newly developed
compounds.
• The project will provide new information on how potential
antivascular therapies shall be evaluated in the clinic.
This includes the development of surrogate markers to
evaluate therapeutic effi cacy.