Prostate Cancer – New Predictive & Therapeutic Options with TRAIL
Prostate Cancer – New Predictive & Therapeutic Options with
TRAIL
One of the human body's protective mechanisms initiated by the
TRAIL protein is massively altered in prostate cancer cells – yet the
same protein seems to improve the survival prospects of patients.
These outstanding results of a cooperative venture between the
Clinical Program on Urological Tumours at the Medical University
of Vienna and Harvard Medical School, USA, have just been
published. They show that the TRAIL protein opens up the prospect
to a more accurate prediction of the disease’s course, as well as
the opportunity to identify a new intervention point for innovative
therapies in advanced prostate cancer.
(firmenpresse) - Even for cancer cells, life can be hard: The body fights them
using many and varied mechanisms. The TRAIL protein (TNF-
Related Apoptosis Inducing Ligand) stimulates a particularly
complex mechanism that ends with the self-destruction, or
apoptosis, of a tumour cell. Numerous other proteins are also
involved in this protective mechanism, and the role of these
proteins in prostate cancer has now been closely analysed in a
joint project between the Clinical Program on Urological
Tumours at the Medical University of Vienna, Harvard Medical
School, Boston, and Mount Sinai School of Medicine, New York
– with surprising results.
Survival through TRAIL
This comprehensive project involved the examination of protein
patterns (that is the frequency of certain proteins) in 200 prostate
tissue samples. Prostate carcinoma patterns were compared
with those of healthy prostate tissue: the unequivocal nature of
the differences found surprised even the director of the Clinical
Program on Urological Tumours, Prof. Michael Krainer: "In 99.5
per cent of all cancerous tissue examined, the protein patterns
showed reduced activity of the TRAIL reaction pathway." In other
words, the anti-tumour protection provided by TRAIL was
compromised in these tissues. This alone shows that TRAIL
plays an important role in the development of prostate cancer.
However, the team found another result to be just as striking: an
increased concentration of TRAIL proteins in the immediate
vicinity of the tumour increases the recurrence-free survival of
patients – an effect that revealed itself to be independent of other
prognostic markers. "This may make it possible to predict the
future course of the disease using TRAIL measurements",
according to Prof. Krainer. "And this result is also an impressive
confirmation of the protection that can be provided by the TRAIL
protein."
It is that very protection that new TRAIL-based therapeutic
interventions seek to exploit. Consequently, tests are currently
ongoing on agents that seek to activate the body's TRAIL-
dependent protective mechanism. In a well-received publication
on ovarian cancer in 2005 Prof. Krainer showed the importance
of a detailed understanding of the reaction pathway in order to
achieve effective interventions. He identified two strategies used
by cancer cells to evade the destructive effect of the TRAIL
protein.
In order to gain a better understanding of the complex TRAIL
reaction pathway in prostate cancer, the international team
analysed the frequency of six TRAIL-relevant proteins in tumours
and healthy tissue. TRAIL itself was studied, along with the two
receptor proteins DR4 and DR5, which bind TRAIL and induce
cell death. Receptors DcR1 and DcR2, which bind TRAIL but do
not initiate cell death, were also included. These "decoy
receptors", as they are known, effectively intercept TRAIL,
protecting tumour cells from its action. This effect is shared by
FLIPL, a protein that was also analysed by the team.
Prognosis and treatment
In point of fact, this detailed analysis revealed a differentiated
image of the TRAIL reaction pathway. In 99.5 per cent of cancer
tissue with reduced reaction pathway activity, the cause of
reduced activity was not at all uniform. In some cases, less DR4
and DR5 were detected, and in other cases there was more
FLIPL. In other cells, even both effects were found. Further
results showed a correlation between the loss of DR4 and DR5
receptors and the Gleason score – a histological classification of
the degree of change in prostate tissue. Another finding
revealed that tissue samples from men over 60 had significantly
fewer DR4 and DR5 receptors.
This collaboration between Austrian and American scientists
clearly shows the importance of the TRAIL reaction pathway in
prostate cancer – and that it may provide a basis for predicting
the course of the disease as well as for designing new therapies.
Original article: Recurrence Free Survival in Prostate Cancer is
Related to Increased Stromal TRAIL Expression. M. Anees, P.
Horak, A. El-Gazzar, M. Susani, G. Heinze, P. Perco, M. Loda, R.
Lis, M. Krainer, and W. K. Oh. CANCER, September 2010
Vienna, 21 September 2010
Themen in dieser Pressemitteilung:
Unternehmensinformation / Kurzprofil:
Scientific Information:
Prof. Michael Krainer
Medical University of Vienna
1090 Vienna, Austria
T +43 / 664 / 183 76 77
E michael.krainer(at)meduniwien.ac.at
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Mariannengasse 8
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E contact(at)prd.at
Datum: 22.09.2010 - 10:12 Uhr
Sprache: Deutsch
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