How to Engineer and Kill a Tumor

Fibronectin has been identified as a key extracellular matrix component of the pre-metastatic niche. High fibronectin expression has been associated with tumor aggressiveness and poor clinical outcomes. Interestingly, we have identified that fibronectin can signal through a paracrine, autocrine, and endocrine manner, and the route of signal transmission is dependent on the stage of the metastatic cascade. In this talk we will describe the development of a modular 3D culture platform that can be used to interrogate the role of fibrillar fibronectin on cancer cell migration and dormancy. Using this platform, we will also describe the creation of an engineered pre-metastatic niche that can be used to create patient-specific model tumors for pre-clinical drug screening. As effective delivery of chemotherapeutic drug dosages is paramount to effective treatment, we will also discuss the use of medical imaging systems for the rational design of controlled release systems. To this end, we will describe the use of diffusion weighted magnetic resonance imaging techniques for in situ characterization of in situ forming implants. These controlled release vehicles are liquid solutions outside of the body, but transition into solid drug eluting depots upon exposure to an aqueous environment. Through the use of diffusion weighted MRI, we are able to track the spatio-temporal changes in diffusivity within the implants. Using this data, we can inform mathematical models that aid in the rational design of the controlled release systems. Ultimately, the use of these technologies will enable better preclinical analysis and inform the design of safer, more effective therapies.