The main goal of this proposal is to develop a robust 3D model of multicellular tumor spheroids (MTS) on an electrospun fibrous scaffold that mimics the tumor microenvironment (TME) and characterize and test its potential for predicting and testing the clinical efficacy of lead anticancer drug candidates. A number of 3D models have been developed to overcome the limitations of 2D cell culture assays, however these models are cumbersome, expensive and do not closely mimic solid tumors in vivo in relation to their interactions with stroma. Transgenex Nanobiotech Inc. (TGN) in collaboration with the University of South Florida has developed a nanofiber scaffold (FSSTM) that enables development of spheroids from single tumor cells and allows co-culturing with a variety of cell types. Technical objectives in Phase 1: (1) develop an FSS-induced 3D MTS model incorporating different human breast cancer cells, endothelial cells and fibroblast cells and characterize TME features and potential for high-content screening, and (2) develop criteria for predicting and testing clinical efficacy using two different breast cancer cell lines that differ in drug sensitivity. TGN is fully poised to develop a high-throughput FSS platform and commercialize this for anticancer drug discovery and drug development.
Project Terms: Adhesions; Antineoplastic Agents; Biological Assay; Biological Markers; Breast Cancer Cell; Cancer cell line; Cell Culture Techniques; cell type; Cells; clinical efficacy; Coculture Techniques; Collaborations; Development; drug candidate; drug development; drug discovery; drug sensitivity; Endothelial Cells; Extracellular Matrix; Fibroblasts; Florida; Goals; Growth Factor; in vivo; lapatinib; Lead; macrophage; Methods; Metric; Modeling; nanofiber; neoplastic cell; Pharmaceutical Preparations; Phase; prototype; Roche brand of trastuzumab; Sampling; scaffold; screening; Solid Neoplasm; Testing; three-dimensional modeling; tumor; tumor microenvironment; Universities
