Cancer Research - Europa

PROMET
Prostate cancer molecular-oriented
detection and treatment of minimal
residual disease
Summary
Keywords | Prostate cancer | micrometastasis | minimal residual disease | bioluminescence | multiphoton microscopy |
nanotechnology | optoacoustic technology | detection | treatment | MegaFasL | human glandular kallikrein 2 |
In the European Union, about 200 000 men are diagnosed
with prostate cancer every year and that number is likely to
increase due to a growing population at risk due to ageing.
Because of the progress made in the treatment of the primary
tumour, mortality in cancer patients is increasingly linked to
metastatic disease, often hidden (micrometastasis or ‘minimal
residual disease’) at the time of diagnosis/therapy of the
primary tumour. Understanding the complex mechanisms of
metastasis (circulating tumour cells – micrometastasis –
metastasis) at the molecular and physiological level is crucial
for the successful detection of minimal residual disease and
for evolving possible strategies for the prevention of their
development into overt metastasis.
In this project, we intend to elucidate the mechanisms and
signature of minimal residual disease in prostate cancer and
develop novel therapeutic approaches to prevent the development
of minimal residual disease to overt metastasis.
In close collaboration of basic scientists with clinical researchers,
the pathways of minimal residual disease will be
explored using functional genomics and expression profi ling
as technology platforms, advanced experimental models
of minimal residual disease using bioluminescence, multiphoton
microscopy, nanotechnology and optoacoustic
technology for detection and treatment. Innovative imaging
and therapeutic strategies developed by the industry
and selected for their potential to enhance detection and
eradicate minimal residual disease will be tested in preclinical
models for subsequent clinical evaluation.
The goal is to identify at least two signal transduction targets,
to develop a diagnostic test for the detection of the presence
of minimal residual disease and to defi ne a novel therapeutic
strategy for the treatment of this disease in prostate cancer.
Thus, earlier detection and diseasespecifi c treatment may
decrease morbidity and mortality, and ultimately have an
impact on socio-economical costs.
Problem
Prostate cancer is one of the most common malignancies in
men: in Europe approximately 40 000 men die of it each
year. Due to the aging population, this number will increase
signifi cantly to around 60 000 men by the year 2020. Therefore,
prostate cancer is a major medical problem with which
the European Community will be increasingly confronted in
the forthcoming decades. There are a number of initiatives
ongoing to reduce the mortality by detecting the disease
earlier, the so-called screening programmes.The clinical
evaluation of the usefulness of prostate cancer screening is
being examined in the European randomised study of
screening for prostate cancer and is expected to answer this
question sometime in 2006. Even though there is a signifi -
cant stage migration in the patient population identifi ed
with this disease, mortality has still not dropped in Europe.
This is primarily because when the tumour has locally
spread, no curative intervention is available. If the patients
are given the time to live, they will ultimately develop bone
metastatic disease that is unresponsive to the currently
available androgen ablation-based therapies. Bone metastases
cause considerable morbidity characterised by severe
bone pain and high incidence of skeletal, neurological and
haematopoietic complications (hypercalcaemia, fracture,
spinal cord compression and bone marrow aplasia). These,
together with the chronic character of terminal CaP disease,
have a severe impact on the socio-economical costs
for healthcare.
The objective of this project therefore meets directly with
one of the priorities of the life science health programme,
namely to combat a major disease, in this case prostate cancer.
Prostate cancer is rather unique in its clinical behaviour
and its molecular genetic background. Relatively few consistent
mutations have been found, which do not occur in
other cancers, so many cases of indolent tumours are
described.
Aim
Because of the progress made in the treatment of the primary
tumour by surgery or radiotherapy, mortality in
cancer patients is increasingly linked to metastatic disease.
Malignant tumours are known to be heterogeneous, and
subpopulations with diff erent invasive and metastatic
potential may alter their biological properties over time and
under treatment due to genetic instability and epigenetic
infl uences.
150 CANCER RESEARCH PROJECTS FUNDED UNDER THE SIXTH FRAMEWORK PROGRAMME