Engineering the Vascular Tumor Microenvironment

Cancer drug development remains a costly and inefficient endeavor that often translates to limited clinical success. While most therapies focus on stalling the growth of or eradicating tumor cells directly, the microenvironment in which these cells inhabit plays a hugely influential role in defining drug efficacy and disease progression. The supporting vasculature system as well as the interstitial extracellular matrix are particularly consequential to the transport, distribution, and uptake of therapeutics. While it is known that the host microenvironment may enable the advancement of malignancy and even the development of resistance, much of the mechanistic understanding by which this regulation occurs remains unclear. This is due in part to a lack of physiologically relevant models, though advancements in the emerging field of "tumor engineering" are beginning to challenge this. The transition away from incompatible animal models and simplified two-dimensional cultures has brought about the creation of advanced three-dimensional models in order to better simulate and test the microenvironmental characteristics that define human cancers. Nonetheless, few systems are able to capture the full range of authentic, complex in vivo events such as neovascularization, intravasation, and variable oxygen distribution. This work will explore the details of developing biologically-inspired, highly controlled in vitro tumor microenvironments to replicate and investigate these events. Such systems have the potential to mediate successful translation of preclinical research to clinical significance, while also providing mechanistic insight into the early stages of tumor progression and metastasis