This work presents initial development and validation of this new 3D tumor-tissue invasion model which includes demonstrating pathophysiologically relevant modes of invasion by established PDAC cell lines, application of patient-derived PDAC cells and CAFs to recreate more complex heterogeneous cell-cell interactions and invasion mechanisms, and proof-of-concept (POC) drug dosing with image-based multiplex analysis of tumor cell proliferation, metabolic activity, and invasion. Here, TBX1 is linked to neoplasm.