Controlled Three-Dimensional Tumor Microenvironments Recapitulate Phenotypic Features and Differential Drug Response in Early vs Advanced Stage Breast Cancer

Progression to advanced stage metastatic disease, resistance to endocrine therapies, and failure of drug combinations remain major barriers in the breast cancer therapy. Tumor microenvironments play an important role in progression from non-invasive to invasive disease as well as in response to therapies. Development of physiologically relevant, three-dimensional (3D) controlled microenvironments that can reliably recapitulate tumor progression from the early non-invasive to advanced metastatic stage will contribute to our understanding of disease biology and serve as a tool for screening of drug regimens targeting different disease stages. We have recently engineered physicochemical microenvironments by precisely controlling the size of 3D microtumors of non-invasive T47D breast cancer cells. We hypothesized that the precise control over physiochemical microenvironments will generate unique molecular signatures in size-controlled microtumors (small 150 μm vs large 600 μm) leading to differential phenotyp...