Until today 20-95% of cancer patients (depending on tumor type) die of systemic metastasis although they have been operated with curative intent. This indicates that tumor cells left the primary tumor and homed to anatomically distant organs long before diagnosis and surgery - unreachable for the surgeon. Months or years later these disseminated cancer cells may grow into lethal, clinically manifest metastasis. The time period after surgery and before emergence of manifest metastasis has been designated minimal residual disease. This latency stage (also called tumor dormancy) is of particular interest for the understanding of tumor biology and for the development of novel therapies. For example, it is still not fully understood, what mechanisms enable tumor cells to leave the primary tumor, how they survive ectopically and what genetic or epigenetic changes are required for metastastic outgrowth. The understanding of these steps will likely lead to novel approaches in the treatment of cancer. So far minimal residual cancer is treated in a blind fashion. Almost all breast cancer patients, for example, receive adjuvant therapy after complete removal of their primary tumor, although it is not known whether or not the target cells are responsive to the drug administered. The success rates of such therapies are therefore still limited. It is the goal of the group to investigate the stage of minimal residual disease in detail and thereby we hope to contribute to the development of rational therapies that might help to prevent the manifestation of systemic metastases in the future.
The investigation of minimal residual disease is hampered by the extreme low frequency at which disseminated tumor cells, being the putative precursor cells of metastasis, can be detected. On the basis of their tissue origin (being derived from epithelial cells in the primary tumor) single disseminated cancer can be detected in mesenchymal tissues like bone marrow or lymph nodes. However, generally only one disseminated cancer cell can be detected between one million normal bone marrow cells in patients without manifest metastasis. Therefore highly sensitive techniques for molecular analysis are required. For example, a single human cell contains 6 pg DNA, i.e. 10-12 g. Therefore, the technical focus of the group is on the development of new techniques for the molecular genetic analysis of single cells.