In recent years the NKI has made major investments to establish
and further develop a dedicated Mouse Cancer Clinic for therapeutic
intervention studies using mouse models of human cancer.
Various novel approaches to treat cancer have already been
tested in the Mouse Cancer Clinic. The design of the experiments is
guided by both novel insights from basic research and clinical
demands. Over the past years the maximum tolerable dose and
anti-cancer efficacy of various anti-cancer agents that are
frequently used in the clinic such as taxanes, topoisomerase I or
II inhibitors, platinum drugs, or DNA alkylating agents have been
benchmarked for several mouse cancer models. In close collaboration
with pharmaceutical companies and academic partners several novel
anti-cancer agents that are eligible for clinical trials have been
or are being tested in our advanced mouse models. This includes
targeted inhibitors of pathways involved in tumor cell
proliferation, cell death or DNA repair. Moreover, new generation
compounds that represent optimized versions of already existing
drugs are investigated.
The main reason why patients with disseminated cancer die is
resistance or tolerance to systemic treatment. Therefore, one focus
of the Intervention Unit is to understand mechanisms of drug
resistance and to identity therapeutic approaches that circumvent
or reverse resistance. Another central handicap in clinical
oncology is the lack of predictive markers, since many patients
only suffer from the side effects of an unsuccessful treatment.
Hence, a major goal of the Intervention Unit is to use mouse models
to identify biomarkers that predict the response of tumors before
treatment is started. In addition to systemic therapies, we are
also investigating locoregional applications of drugs, surgery or
radiation. The identification and treatment of tumors is greatly
facilitated by dedicated systems for state-of-the-art imaging and
image-guided radiation therapy of small animals.
Preclinical imaging systems are essential for accurate
measurement of tumor growth, metastasis formation and therapy
response in mouse models of human cancer. For this purpose, a
dedicated Imaging Unit has been realized within the Mouse Clinic.
The goal of this unit is to carry out attractive research that
addresses relevant questions encountered by clinical imaging of
cancer patients. This Unit includes a NanoSPECT/CT system (Bioscan)
for combined single-photon emission computed tomography (SPECT) and
computed tomography (CT) imaging, as well as IVIS systems (Caliper
Corp.) for bioluminescence and fluorescence imaging. These systems
are frequently used to measure drug responses of mouse models of
breast, lung or brain cancer and to monitor metastasis formation.
Due to the generous support of the Netherlands Organisation for
Scientific Research, we will upgrade our present equipment in the
coming months, and invest also in magnetic resonance imaging (MRI)
and positron-emission tomography (PET).
In sum, the Mouse Cancer Clinic aims to provide a controlled
environment with state-of-the-art infrastructure for testing of
therapeutic approaches that may subsequently be applied to cancer
More information: www.mccanet.nl
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