Prostate cancer translational research in Europe: the search for
29 June 2009
Collaboration in prostate cancer translational research in Europe is
not only vital to sustain the progress achieved in recent years but also
to streamline current efforts between researchers and clinicians and
avoid duplication or overlaps. This was amongst the goals of the two-day
Prostate Cancer Translational Research in Europe (PCTRE) Meeting which
was held in Amsterdam, The Netherlands earlier this month.
"It is important that people with research background can communicate
with clinicians and vice versa. By doing so we maximise the interaction
amongst specialists. It is essential that we show our results to each
other," said Prof. Peter Mulders (Nijmegen, The Netherlands), chairman
of the European Association of Urology Research Foundation (EAU-RF),
organiser of the PCTRE meeting.
With more than 170 participants, the conference opened with lectures
and updates on the work of prostate cancer consortia based in Europe.
Within the European Community-based framework programme these consortia
received around €40 million in funding covering scientific topics such
as the search for diagnostic and prognostic markers for prostate cancer.
Dr Thorunn Rafnar (Reykjavic, IS) spoke on the current work regarding
the identification of common genetic variants that affect the risk of
prostate cancer. 42% of prostate cancer has a genetic cause. The
lifetime risk of a man in the European Union to acquire prostate cancer
is 10% and it is the third leading cause of death from cancer in men.
"First risk models including low risk variants are appearing," Rafnar
said as she added that "the search for genetic determinants of disease
severity is ongoing."
Polygene, one of the participating consortia, uses Genome-wide
Association studies (see www.genome.gov) to analyse genomes responsible
for cancers of the prostate and breast. However, current genetic risk
models do not predict who will get progressive disease. Promark, another
consortium, searches for genetic variants that do associate with
aggressive cancer forms.
She also noted that the information on PSA genetics may improve
utility in screening. Rafnar also pointed out that although "...much
work remains…. finding causative variants at known loci define
The lecture by Prof Freddie Hamdy (Oxford, UK), 'What is the best
practice in bio-banking?’ focussed on the dilemmas in prostate cancer
(how to identify the population at risk, how to prevent overtreatment
and treatment failure).
“We can treat, we can cure, but who should we treat and cure?”, he
said. Collection and cohorts of prostate cancer samples are important in
order to look for new biomarkers. But the search for prognostic markers
needs a multi-targeted approach. “The focus should be on the benefit to
the patient; it should result in eg a reduction in mortality or of side
effects”, says Hamdy.
Dr Schenk-Braat (Rotterdam, NL) says: “The incidence of prostate
cancer will increase and PSA is not a sensitive enough tool to identify
men at risk”. The P-Mark project evaluates promising biomarkers and has
selected 3: osteoprotegerin (a bone turnover protein discovered by the
group of Prof Hamdy), PCA3 (Jacques Schalkens (Nijmegen, NL) group) and
multikallikreins (project of Profs Lilja (New York, US) and Petterson).
An across-marker validation study is ongoing. “We can name the
European prostate biobank, increased support of the validation of
biomakers and the prostate risk indicator as a few results from the
P-Mark project”, says Schenk-Braat.
In another update lecture, Dr O Kallioniemi (Helsinki, Finland)
discussed the integration of high-throughput technologies to identify
drug targets and new therapeutic options for prostate cancer. Amongst
his conclusions are:
- Majority of anti-cancer drugs are equally effective in
cancer and control cells.
- TSA, thiram, disalfiram and monensin (are) identified as
cancer selective compounds inhibiting VCaP cell growth at nanomolar
- In vivo studies using VCaP cell xenografts showed reduced
tumour growth in response to disulfiram exposure; disulfiram was not
able to block tumour growth indicating the need for combined
- Disulfiram induced metallothionein expression, knockdown
of MTI increased efficiency by five-fold.
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