A TISSUE ENGINEERING APPROACH TO THE DEVELOPMENT OF AN IN VITRO 3D TUMOR MODEL FOR DRUG DELIVERY STUDIES

Abstract

The lack of good preclinical models has hampered anticancer drug discovery. Standard preclinical protocols require the growth of cells in high throughput two-dimensional culture systems. Such in vitro drug testing methods yield drug efficacy results that differ greatly from animal models. It is conceivable that three-dimensional growth may be responsible for some of these changes and that such growth may form a reproducible and more representative step in tumoricidal validation prior to animal implantation. The role of three-dimensional culture on angiogenic potential and tumor growth was studied and high throughput anticancer or anti-angiogenic drug screening was also carried out. A co-culture model with immortalized fibroblasts and endothelial cells was used to study the effects of the supporting stroma on cancer cell behavior. The tumor constructs were cultured in a bioreactor with replicated interstitial fluid pressure, and these constructs were found to closely approximate the subcutaneous tumors in SCID mice.