GRK 2154 - Materials for Brain

P8: Neuroimplants for glioblastoma therapy (J. Held-Feindt)

Glioblastoma multiforme (GBM) is a poorly curable disease due to its heterogeneity that enables single cells to survive treatment regimen and initiate tumor regrowth. Although some progress in therapy has been achieved in the last years, the efficient treatment of GBM is still a clinical challenge. Therefore, the development of new therapeutic strategies including alternative drugs and drug-carrier tools, especially for the local treatment of (residual) tumor cells in the tumor cavity, is mandatory. In the last years, we learned in more detail, how GBM cells respond to/ elude from different chemotherapeutic treatment strategies, e.g. by switching into a chemoresistant dormant cell state. Thus, we developed treatment plans, which may be helpful to overcome these tumor escape mechanisms. We showed that sequentially applied single and combined chemotherapeutic treatment yields higher cytotoxicity and better tumor growth control in a long-term stimulation GBM in vitro model. Further, we established an in vivo adapted GBM co-culture model which enables us to mimic in vitro the complete and incomplete GBM resection and gives us the possibility to test material-drug combinations for especially local treatment strategies. In close contact with the material scientists, we developed micro-structured, functional materials as drug carriers and investigated the material-controlled drug release and cytotoxic effects on GBM cells in vitro.
Further investigations will focus on material-drug combinations, which will be examined in vitro under individualized patient-specific topics in our in vivo adapted GBM co-culture model with a specific view on the (possible) initiation of tumor escape mechanisms like dormancy. In parallel, promising material-drug combinations will be further improved, tested in applicable GBM in vitro (primary) cell culture assays, and adapted for the in vivo use. In close collaboration with a neurosurgeon, working as a clinical scientist in this project, patient-related data linked to the in vitro GBM assays will be acquired. A GBM complete/ incomplete resection in vivo rodent model will be established and promising material-drug combinations will be transferred to this model for in vivo evaluation of efficiency and usability of developed material-drug combinations. For all investigations state-of-the-art methods of cell biology, molecular biology and protein biochemistry will be used. All investigations will be performed in close collaboration with different groups of material scientists, physicians and natural scientists, combining the expertise of different disciplines.