UC Irvine

Treatments for cancer remain elusive due, in large part, to the dynamic and unstable genome of most cancer cells. More recently it has become evident that tumor growth and progression to metastasis depends on the ability to recruit normal cells, such as endothelial cells, fibroblasts, as key accomplices. These observations suggest that selective targeting of normal cells, which have a stable genome, could be an effective alternative or complimentary approach in the overall management of the disease. Understanding of such relationship is key for the design of anti-metastatic therapeutics. However, much of the data reported in this field has been performed in xenograft models and/or 2D cultures; which are limited by the number of controllable variables, extrapolation to human tumor physiology, and not amenable for a high-throughput design. This work aims to address the role of the tumor microenvironment using a novel in vitro platform that combines microfluidic and tissue engineering technology to create a 3D tumor microarray in which the tumors receive their nutrients through perfused human microcirculation. This model is capable of replicating the physiology of the in vivo tumor microenvironment; thus providing relevant physiological results. Most importantly, the impact of creating an in vitro 3D metastasis model with perfused human capillary bed could significantly enhance high-throughput anti-metastatic drug screening.