Establishment of a marker panel for early therapy response of tumor and stroma in a optimized 3D tumor stroma model

• Applicants: Professor Dr. Hans-Peter Deigner; Professorin Dr. Margareta M. Müller
• Subject Area: Hematology, Oncology ; Cell Biology
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 518861811

Cancer is the second most common cause of death in industrialized countries with its frequency increasing continuously due to the steady increase in life expectancy. In light of the demographic change in industrialized societies the development of efficient cancer therapies is therefore essential. However, the process from candidate substance to successful cancer therapeutics is not only time consuming but also very costly. Reduction in time and cost could be achieved by an optimized prediction of efficacy already in early stages of drug development. Up to date drug candidates are still predominantly tested in 2D culture models or simple spheroid systems that do not allow a prediction of efficacy in the tissue context of the tumor and its microenvironment. Thus, they disregard a crucial aspect of tumor development and progression, leading to frequent failure of hopeful candidates later in the development process. Consequently, analysis in complex 3D models that reflect tumor and microenvironment as well as the establishment of a reliable marker panel for therapy response is indispensable for successful prediction of drug efficacy. The predominantly simple 3D models that are currently in use in pharmaceutical testing only allow the analysis of effects on tumor cells alone or isolated components of the stroma and do not include the complex interaction between tumor cells, stroma and angiogenesis. The few more complex models that exist lack the potential for standardization that is vital for pharmaceutical testing. This project therefore uses a standardized 3D tumor stroma model based on a chemically defined hydrogel matrix that combines micro tumors of GFP-transfected glioblastoma and colon-, head and neck-, mama- and lung carcinoma with stromal fibroblasts, inflammatory cells and RFP-transfected endothelia cells. The system allows for the first time to recapitulate the “angiogenic switch” without addition of external mediators of angiogenesis. Using this model and employing the equipment obtained in another DFG proposal, the project aims at characterizing the morphological changes in the tumor and stroma-compartment under therapy and will establish a reference panel of markers for early and established therapy response during anti-tumor or anti-proliferative as well as anti-stroma and anti-angiogenic therapy.

• DFG Programme: Research Grants