Many anticancer drugs fail in human trials despite showing efficacy in in vitro studies and animal models. It has become clear that the in vitro assays involving 2D monoculture do not reflect the complex cellular and matrix microenvironment of the tumor tissue and this may explain the failure of 2D models to predict clinical efficacy. The goal of this study is to develop an in vitro tumor-aligned 3D coculture model representative of the human tumor tissue architecture using breast cancer, stromal, and endothelial cells and test this model with known effective anticancer drugs. The first objective it to optimize the composition of the extracellular matrix and the cell model to elicit the physiogical tumor morphology, proliferation, invasion, stromal recruitment, and endothelial sprouting . The second objective of this contract is to characterize changes in gene expression for this model compared to traditional 2D and 3D culture models using RT-PCR, Western Blot, and Immunocytochemistry. The third objective of this contract is to validate the model as effective by evaluating these physiological properties in response to Fluorouracil and Paclitaxel. Successful implementation of this model would save significant cost and time for drug development, ultimately benefiting the patient and society.
