Metastasis, cancer spread to other organs, is the principle cause of death of cancer patients. Early detection of metastatic tumor cells, development of new treatment strategies and knowledge about how to prevent cancer metastasis are some of the most cha llenging tasks in cancer research. Our project is addressing aspects of these problems, spanning from studies on biological and molecular aspects of metastatic proscess, development of methods for detection and characterization of circulating, micrometast atic tumor cells, and evaluation of new methods for treatment.
To study the interplay between malignant and normal cells that characterize metastasis formation we have established several animal models mimicking human cancer, and in the proposed project w e will use these models and clinical material for in vivo imaging of secondary tumor formation, for expression profiling aimed at identifying molecular signatures predicting organ-preferred metastasis, and for evaluating principles of targeted therapy.
Us ing immunomagnetic and fluorescent beads combined with a semi-automatic capillary system we can prepare pure tumor cell fractions from bone marrow samples, and use the selected cells in high throughput analyses (RNA or protein) for molecular comparison of primary, metastatic or micrometastatic cells, making it possible to identify novel genes involved in the metastatic process or of importance for predicting prognosis or therapeutic effects. Functional studies on interesting protein candidates will be per formed.
We have developed an immunotoxin which is now in clinical phase I trial, and in parallel we study its effects with emphasis on induction of apoptosis. In this and other trials, we also monitor the effect by using micrometastasis in bone marrow as a surrogate marker