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 patients.