Malignant transformation of the breast and other organs is invariably associated with dramatic alterations in the microenvironment surrounding neoplastic cells. An integrative view of neoplastic progression must take into account both the accumulation of genetic mutations and the role played by microenvironmental signals. That is, I believe the eventual development of a neoplastic lesion is governed by dynamic interactions between mutant cells and the three-dimensional (3D) organization of the epithelial tissue in which they reside. To test this hypothesis, my group uses sophisticated 3D culture models of the mammary epithelial duct to analyze quantitatively the reciprocal feedback between tissue architecture and neoplastic progression. These lithography-based models enable micrometer-resolution control of tissue geometry and microenvironment, and
provide quantitative 4D data in a physiologically relevant context. I expect our findings to unveil the role of tissue architecture on neoplastic selection, which could have significant impact for discovery and evaluation of novel therapeutic targets to combat tumor progression.