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P-MARK<br />
Validation of recently developed<br />
diagnostic and prognostic<br />
markers and identifi cation of novel<br />
markersfor prostate cancer using<br />
European databases<br />
Summary<br />
The current diagnostic markers for prostate cancer have<br />
a low specifi city and lead to over-diagnosis and overtreatment<br />
due to the detection of small non-aggressive or<br />
non life-threatening cancers. In addition, there are currently<br />
no effi cient serum or urine markers available for the prognosis<br />
of this malignancy. The P-Mark project will address<br />
the growing need for improved diagnostic and prognostic<br />
markers for prostate cancer.<br />
Problem<br />
Keywords | Prostate cancer | markers | diagnosis | prognosis | serum | urine | proteomics | mass spectrometry |<br />
In Europe, prostate cancer (Pca) is the second most frequent<br />
lethal malignancy in men. Yearly about 40 000 men<br />
die of Pca in the EU countries. There is a slow increase of<br />
mortality and in addition, due to an ageing population,<br />
a 50 % increase in incidence is expected by 2020. So far, the<br />
only chance for cure is early detection and treatment by<br />
either surgery or radiotherapy. Diagnosis of Pca is made by<br />
ultrasound-guided transrectal biopsy of the prostate for histology.<br />
An increased level of the serum marker prostate<br />
specifi c antigen (PSA) often signals the presence of prostate<br />
cancer and the need to perform such a biopsy. A major<br />
disadvantage of this diagnostic marker is its low specifi city,<br />
resulting in a signifi cant amount of false biopsy indications.<br />
PSA is a normal excretion product of the prostate cells and<br />
is therefore not only found in the circulation of men with<br />
prostate cancer but also of men with a normal prostate and<br />
men with benign prostatic hyperplasia, a phenomenon that<br />
is associated with ageing. Nevertheless, PSA is the standard<br />
marker for Pca diagnosis and has been demonstrated to be<br />
eff ective in advancing the diagnosis by detecting Pca at<br />
earlier stages. A growing number of men choose to be<br />
screened for Pca by PSA analysis, even up to 60-70 % of<br />
men in the USA. However, the value of screening for Pca has<br />
not been established yet and is currently the subject of<br />
investigation in the European Randomised Study of Screening<br />
for Prostate <strong>Cancer</strong> (ERSPC). A major drawback of the<br />
standard diagnostic tools for Pca is the detection of small<br />
non-aggressive or non life-threatening cancers, leading to<br />
over-diagnosis and over-treatment, as well as the detection<br />
of tumours that are too advanced to cure. Currently, there<br />
are no serum or urine markers available for the prognosis of<br />
Pca at early disease stages apart from PSA. It is apparent<br />
that improved diagnostic and prognostic serum or urine<br />
markers are required that can discriminate men with clinically<br />
irrelevant Pca, curable Pca, or life-threatening Pca.<br />
Aim<br />
For three years, P-Mark will search for improved diagnostic<br />
and prognostic Pca markers by the identifi cation and evaluation<br />
of novel markers as well as the evaluation and validation<br />
of recently developed promising markers. Novel serum and<br />
urine markers will be identifi ed in clinically well-defi ned biomaterials<br />
using innovative mass spectrometry tools, and<br />
antibody-based immunoassays will be developed for these<br />
markers. The novel markers will be evaluated for their clinical<br />
importance using these assays. Recently developed, promising<br />
markers that prove their clinical value during the evaluation<br />
will be validated on a sample set derived from two European<br />
screening studies (the ERSPC study and the ProtecT study).<br />
Eventually, the markers arising from this project will be off ered<br />
to SMEs for commercialisation and to ongoing large European<br />
clinical studies for clinical implementation.<br />
Expected results<br />
• The establishment of a serum biorepository and a urine<br />
biorepository for the discovery, evaluation and validation<br />
of diagnostic and prognostic Pca markers.<br />
• The discovery of novel Pca markers in human body fl uids<br />
by innovative mass spectrometry tools.<br />
• The establishment of the clinical utility of recently developed<br />
promising Pca markers, including PCA3DD3, bone<br />
morphogenetic protein-6 (BMP-6), osteoprotegerin<br />
(OPG), nicked PSA, human kallikrein 2 (hK2) and cytochrome<br />
P450 3A5*3 polymorphism (CYP3A5*3).<br />
• The validation of Pca markers and identifi cation of risk<br />
groups in the general population in Europe.<br />
• The development of guidelines for cost-effi cient strategies<br />
for Pca detection and therapy.<br />
146 CANCER RESEARCH PROJECTS FUNDED UNDER THE SIXTH FRAMEWORK PROGRAMME
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