Cancer Research in Switzerland - Krebsliga Schweiz

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Körner Meike | In vitro evaluation of the glucagon-
like peptide 2 receptor expression in human cancer:
Molecular basis for in vivo tumor radiotargeting
(OCS 02349-02-2009)
Duration: 01.07.2009 – 01.07.2011
Peptide receptors that are highly overexpressed in human
tumours represent potential molecular targets for important
clinical applications, namely, in vivo peptide receptor
targeting of tumours. Radioactively labelled peptide analogues
that bind specifically to tumoural receptors can be
used for imaging or radiotherapy of tumours. Moreover,
cold, long-acting peptide analogues may interfere with
biologic functions of tumour cells regulated by peptide
receptors, such as hormone release or proliferation.
The glucagon-like peptide 2 (GLP-2) receptor represents
a potential new candidate for such applications. It is closely
related to the glucagon-like peptide 1 (GLP-1) receptor,
which was recently identified as an important clinical target
in insulinomas. The GLP-2 receptor had been of interest
because of its stimulatory role in intestinal growth
and, consequently, potential therapeutic use in short
bowel syndrome. Lately, evidence has emerged on its possible
role in cancer. The GLP-2 receptor was identified
in tumours in single instances. Moreover, in vitro data indicate
that it may stimulate tumour cell migration and
growth. These preliminary results call for an in-depth
evaluation of the GLP-2 receptor for its suitability as tumour
target.
The aim of our project was to perform the first step in that
evaluation, namely, to assess the GLP-2 receptor expression
quantitatively in a large spectrum of human tumours.
We analyzed approximately 200 different human tissue
samples for their GLP-2 receptor expression with in vitro
receptor autoradiography. This method identifies receptor
binding sites, i.e. the actual clinical target, in tissues. It allows
specific receptor identification based on receptor
pharmacology as well as quantification of receptor levels
in tissues. We found a marked GLP-2 receptor expression
in several tumour types mostly of gastrointestinal origin,
in particular in gastrointestinal stromal tumours (GIST).
The binding data were confirmed by RT-PCR. This tumoural
GLP-2 receptor expression represents the molecular
basis for an in vivo GLP-2 receptor targeting of GIST.
In future studies it has to be investigated whether therapy
with long-acting GLP-2 analogues of short bowel syndrome
may affect the biologic behaviour of GIST.
Project coordinator
PD Dr. Meike Körner
Abteilung für Zellbiologie und
experimentelle Krebsforschung
Institut für Pathologie
Universität Bern
Murtenstrasse 31
Postfach 62
CH-3010 Bern
Phone +41 (0)31 632 99 60
Fax +41 (0)31 632 89 99
meike.koerner@pathology.unibe.ch
Kristiansen Glen | Identification of a clinically
applicable prognostic RNA signature of prostate
cancer (KFS 2465-08-2009)
Duration: 01.01.2010 – 01.01.2012
A major problem in the treatment of prostate cancer relates
to the difficulty in estimating tumour aggressiveness.
This probably leads to over-treatment in up to 35 % of
prostate cancer patients. Unfortunately, current clinical or
histopathological approaches are still unsatisfactory with
regard to predicting the aggressiveness of prostate cancer.
The aim of our study is to develop and validate novel,
mRNA-based methods that will allow estimation of prostate
cancer prognosis. In previous studies the applicant
identified several mRNA-based markers that are prognostically
relevant. Modern high-throughput technologies allow
their measurement simultaneously in many tumours.
By comparing expression profiles in retrospective samples
representing both aggressive and indolent tumours, combinations
of markers or profiles will be developed that aid
estimation of the risk of individual prostate cancers to
progress and eventually lead to the patient’s death or stay
benign. In future, this approach may become an important
tool for physicians that would allow them to apply
tailored therapies to each patient based on a personal risk
profile.
Project coordinator
Prof. Dr. Glen Kristiansen
Institut für klinische Pathologie
UniversitätsSpital Zürich
Schmelzbergstrasse 12
CH-8091 Zürich
Phone +41 (0)44 255 34 57
glen.kristiansen@usz.ch
Mermod Nicolas | Evaluation of AP2 protein-binding
microarrays for breast tumor profiling and for
the prognosis of the response to chemotherapies
(KFS 02446-08-2009)
Duration: 01.01.2010 – 01.01.2013
In Switzerland, about 5,000 new cases of breast cancer
are recorded each year, and despite significant progress,
about 1,500 patients still die of this pathology. This is a
very heterogeneous disease whose accurate classification
remains difficult. Although the diagnosis makes it possible
to tailor treatment to individual cases, some tumours do
not respond to the therapy, and it is generally difficult to
predict with certainty whether a treatment will be effective
for a given patient. With the ability to predict the lack
of therapeutic response in case of neoadjuvant therapy
(chemotherapy before surgery), unnecessary treatments
could be avoided and the patient could be operated on
without undue delays. Most molecular methods investigating
tumour biology are exploring solely DNA, mRNAs
or proteins, and they are often unaware of the activity or
functional interaction of proteins with each other and
with target genes. In this project, we hope to develop an
approach based on analyzing the interactions of proteins
from the tumour with the genes responsible for tumour
progression and resistance to chemotherapy, so as to provide
a more comprehensive analysis of the tumour type
and to potentially better predict its treatment response
potential.