Cancer Research - Europa

Keywords | Neuroblastoma | medulloblastoma | retinoblastoma | nephroblastoma | rhabdoid |
Ewing | translational research |
E.E.T.-Pipeline
European Embryonal Tumour Pipeline
Summary
Treatment of embryonal tumours (ET) is a challenge for the
pediatric oncologist. Innovative translational research is
required to exploit available genomic data and implement
state-of-the-art technologies to overcome the defi cits of
current diagnostic and treatment strategies. We will set up
a Consortium of leading European institutions and SMEs
with extensive clinical and technological expertise in order
to establish a unique pipeline for the comprehensive development
and validation of novel diagnostic tools in addition
to effi cient preclinical drug development for ET.
Our holistic approach includes:
• validation of a chip-based diagnostic platform tailored
specifi cally for ET, including analysis of genes previously
shown by the Consortium to be aff ected in ET;
• validation of a chip-based diagnostic platform tailored
specifi cally for ET, including analysis of genes previously
shown by the Consortium to be aff ected in ET;
• extension of an existing database designed to warehouse
complete clinical and experimental data for
neuroblastoma to include all ET entities;
• implementation of a virtual ‘ET-Biobank’ to improve
sharing of patient samples;
• functional characterisation of the most promising molecular
targets previously identifi ed by the partners as
a foundation for entry into a drug development pipeline;
• integration of existing disease-specifi c mouse models
to evaluate new treatment modalities in vivo;
• initial evaluation of a screening method and antibody
aff ecting ET cell invasion;
• application of novel bioinformatic solutions for meta-
analysis;
• dissemination of the novel tools to researchers and
clinical study centres in Europe.
Our coordinated eff ort can achieve the critical mass to
facilitate the necessary integration of research capacities
for translating ET genome data into signifi cant medical
progress. Involvement of clinical study centres will ensure
a direct link to the bedside, aimed at improving child health
and quality of life.
EARLY DETECTION, DIAGNOSIS AND PROGNOSIS
Problem
Second to accidents, cancer is still the leading cause of death
for children in Europe. Approximately 30 % of childhood
malignancies are embryonal tumours (ET), often demonstrating
resistance to conventional treatment approaches and
being associated with lower survival rates compared to other
childhood cancers. Thus, novel diagnostic and therapeutic
options are urgently needed in particular for this group of
tumours in order to improve survival rates and quality of life of
pediatric cancer patients. The limitations of current treatment
approaches include, in particular, a lack of validated postgenomic
technology available for routine diagnostics and
a large gap between target identifi cation in basic research
eff orts and resulting pre-clinical development of novel drugs.
Beyond defi ning characteristic gene expression signatures,
only a limited number of studies have addressed the functional
analysis of identifi ed target genes. The genetic low
complexity of ET tumours provides a suitable system to
identify druggable targets. Conclusive diagnosis using histology
alone is diffi cult due to the uniform morphologies of
the diff erent ET entities, identifying ET as an important area
to complement current strategies with modern post-genomic
approaches.
Our approach is of particular importance for ET, as the ET
entities are orphan diseases, meaning each entity does not
have a large enough market to justify the costs of drug development
by a private company. The identifi cation of potential
targets for all ET entities should be more economically
attractive for private companies. Common molecular pathways
such as myc- and RB-signalling and chromosomal
deletions including 1p36 and 11q loss have been previously
identifi ed in diff erent ET entities by the Consortium members
and others, supporting a rationale integrating all ET types.
Aim
The multimodal genomic and proteomic approaches proposed
here provide a promising alternative for more
successful tumour diagnosis, subclassifi cation and drug
development for ET. This STREP will provide a coordinated
strategy for the translation of basic research results into the
pre-clinical arena, focusing on the implementation of stateof-the-art
diagnostic tools, improvement of access to clinical
material, and the effi cient combination of post-genomic
research approaches with pre-clinical drug development.
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