Cancer Research - Europa

The primary tumour releases a large number of cells into the
blood stream. However, only a small minority (approx. 0.01 %)
of the tumour cells entering the blood are thought to be
capable of developing into metastatic deposits. The future
ability to detect minimal residual disease early, to understand
the natural history of micrometastasis and, consequently, to
predict outcome, and ultimately to treat adequately will rely
on investigational eff orts in a context as close as possible to
the clinical situation. For this a close interaction between
clinical experience and basic research, together with the
availability of human tumour tissue specimens from established
tumour tissue banks and adequate experimental
models are crucial to improve current treatment modalities
or even develop innovative therapeutic strategies. In this targeted
approach to combat minimal residual disease in
prostate cancer, we will pursue various levels at which we
attack the malignant process and validate these at a phenotypic
and functional level. We will be developing novel
means of detecting and treating minimal residual disease.
By integrating a variety of state of the art approaches, we
aim to:
• identify and validate at least two target genes for detection
of minimal residual disease in prostate cancer;
• develop an integral in vivo model of minimal residual disease
allowing the study of the mechanisms and signatures;
• evaluate the in vivo detection of minimal residual disease
by means of nanoparticles and optoacoustics;
• develop a therapeutic strategy for the treatment of minimal
residual disease in prostate cancer.
Expected results
We expect to identify genes up- or down-regulated in minimal
residual disease with a potential for use in diagnostics
and therapeutic strategies. Furthermore, the expression pattern
might increase our understanding of the mechanisms
and reveal potential novel therapeutic targets. With this
work we expect to provide a detection assay with the potential
for use in clinical practice based on blood, urine or bone
marrow aspirate and evidence that optoacoustics can be
applied in the clinical context.
Novel treatment strategies will be developed and we expect
to validate at least one treatment strategy in the treatment
of minimal residual disease (MRD) that can be applied in the
clinical setting. Finally we expect to establish a confocal and
deconvolution-based dorsal chamber metatarsal model for
the study of homing and growth support of minimal residual
disease. Further we intend to establish a dual wavelength
bioluminescent imaging system for the simultaneous study
of two indicators, enabling the evaluation of the interrelation
between these.
EARLY DETECTION, DIAGNOSIS AND PROGNOSIS
Potential applications
The innovative potential and impact on industry, the health
system and the market lies in:
• the development of novel diagnostic methods for the
detection of minimal residual disease;
• the implementation of optoacoustics with the help of
nanoparticles for diagnosis and therapy;
• novel targeted therapeutic strategies for micrometastases
that take into account the particular knowledge about
specifi c biology of the disease gained from animal models
that more closely mimic MRD (translational research);
• the optimisation of experimental imaging of living cells
by coupling multi-photon microscopy with quantum dot
nanoparticle cell tracking to study early pathophysiological
pathways involved in MRD. This will complement
other methods used by the group, such as whole body
animal bioluminescent imaging;
• the development of a more sensitive bioluminescencebased
imaging system for the preclinical investigation of
the biology of minimal residual disease and the in vivo
evaluation of novel diagnostic and therapeutic methods.
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