DISSECT · Disseminating tumor cells as novel biomarkers: Dissecting the metastatic cascade in cancer patients

Breast, prostate, lung and colorectal cancer as solid tumours derived from epithelial tissues are responsible for 90% of all new cancers in Europe. Present tumour staging is mainly based on local tumour extension, metastatic lymph node involvement and evidence of overt distant metastasis obtained by imaging technologies. However, these staging procedures are not sensitive enough to detect early tumour cell dissemination as a key event in tumour progression. Our team has therefore focused on the development of ultrasensitive assays that allow the specific detection and molecular characterization of single tumour cells in bone marrow (DTC) and blood (CTC) of cancer patients. These methods allow the direct assessment of disseminating tumour cells including the detection of therapeutic targets and mechanisms of resistance in patients undergoing therapy. Based on our established network of clinical collaborations, the DISSECT project will detect and characterize DTC/CTC in patients with the four most frequent tumour entities in the EU by high resolution methods. We will investigate representative clinical studies for current interventions that may have an impact on tumour cell dissemination, including diagnostic biopsies, surgical resection of the primary tumour, radiotherapy, chemotherapy and in particular targeted therapies. The technologies for DTC/CTC analyses previously developed by our team will be complemented by cutting-edge technologies and adapted to the analysis to decisive molecular processes underlying the particular intervention. The results obtained in the DISSECT project will provide unique insights into the biology of tumour cell spread in humans and these insights might lead to improved concepts in the clinical management of cancer patients.