Models of treatment and metastasis formation

© Photo Fraunhofer ITEM

The concept of personalized tumor therapy is based on the use of specific, custom-tailored medication to treat an individual’s cancer. Besides comprehensive knowledge about the tumor’s molecular properties, development of such treatment strategies benefits considerably from the use of cell models representing the actual target cells of the individualized therapy. Such cell models are needed to test novel therapeutics and to study the biology of specific tumor cell populations. Tumor cells that have already spread in the body – e.g. disseminated tumor cells (DTC), which are metastatic progenitor cells, and circulating tumor cells (CTC) in the patient’s blood – are important target cells for specific therapy approaches in patients with metastatic disease.

Due to the very low abundance of DTC and CTC and the resulting difficulty to detect and enrich them, it is nearly impossible at present to expand these cells and thereby establish representative models for preclinical drug testing. The use of cell models based on these rare cells, however, will enable a deeper understanding of metastasis formation and improved testing of novel therapeutics.

Our expertise

Preclinical in-vitro/in-vivo models are essential for anticancer drug development. It is becoming increasingly evident, however, that cell models based on the primary tumor provide only insufficient information for treatment of already disseminated tumor cells. In contrast, DTC and CTC are the target cells of such therapies. Fraunhofer ITEM in Regensburg is developing workflows for rare-cell expansion and has already established first in-vitro-/in-vivo models based on DTC or CTC. We are using these models to gain a better functional understanding of DTC and CTC biology and of their response to therapy.

Our methods

© Photo Fraunhofer ITEM

DTC and CTC are very rare tumor cells that can be found in bone marrow and/or lymph nodes or blood of cancer patients. Isolation and expansion of these rare cells pose considerable challenges. In a first step, the few tumor cells have to be separated from healthy cells in the tissue sample. This requires a phenotypic difference (e.g. surface markers or cell size) between tumor cells and healthy cells. In a second step, the tumor cells are cultured under highly specific culturing conditions (in vitro and/or in vivo) that allow unrestricted growth of DTC and CTC. In both these steps, the phenotypic differences between tumor cells and healthy cells, but also the enormous variations in optimal growth conditions between different types of tumors pose substantial challenges. A focus of our work, therefore, is on the development of customized protocols for expansion of DTC and CTC from different organs. In addition, we use the expanded cells to establish preclinical models (in vitro/in vivo) mimicking the specific conditions of the tumor cells’ tissue of origin (e.g. human immune cells). Such models put us in a position to test how these cells will respond to therapy in patients.