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During tumor development, cancer cells actively act on and reshape their surrounding tissue, creating what is known as the tumor microenvironment (TME). The TME presents a complex network of cellular and acellular components that eventually help the tumor to grow, invade the surrounding tissue, escape the immune system and evade treatment. With increased understanding of the TME, novel treatment strategies have been developed that do not focus on killing the tumor cells, such as conventional chemotherapy, but on modulating this TME. Although such strategies seem promising, only a fraction of novel drug candidates reach the clinics and most drugs already fail in early pre-clinical stages. One of the main reasons for this failure is the lack of cell culture (in vitro) models that represent the TME in a biologically relevant fashion that allow to evaluate and optimize novel drug candidates in an efficient manner.