An in-vitro method to study anti-apoptotic signaling from the extracellular environment

The emergence of acquired multidrug resistance (MDR) remains a major hurdle in the successful treatment of cancer. Signaling from the extracellular environment has shown to induce de novo drug resistance, a pre-state to MDR. Hence, identifying such signaling pathways may pave the way for novel targeted therapies that can prevent the occurance of MDR. This creates a demand for a predictive in vitro method for the study of the dependence of anti-apoptosis signaling on the environment. So far, in vitro studies of the effect of environmental parameters on drug response have typically focused on one parameter at a time, such as the interaction with matrix proteins or the effect of enhanced cell-cell contacts in 3D organized cells. Therefore we are working on an in vitro platform, with which it is possible to simultaneously study the effect of several extrinsic parameters. This platform consists of a microwell array molded into a polyethylene glycol (PEG) hydrogel. The material properties of this hydrogel make it possible to mimic tissue-like stiffness. This allows us to explore many parameters of the environment, such as dimensionality, composition of the interfacing protein matrix and rigidity.