Search for prostate cancer biomarkers continues

"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."

Focus on dilemmas

Polygene, one of the participating consortia, uses Genome-wide Association studies 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 functions."

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 e.g. a reduction in mortality or of side effects", says Hamdy.

Integration

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 biomarkers 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 concentrations.
• 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 approaches.
• Disulfiram induced metallothionein expression, knockdown of MTI increased efficiency by five-fold.

www.uroweb.org/