Impact of the spheroid model complexity on drug response

摘要: Pharmaceutical investigators are searching for preclinical models closely resembling the original cancer and predicting clinical outcome. This study compares drug response of three in vitro 3D-drug screening with different complexity. Tumor cell line spheroids were generated from lines Caco-2, DLD-1, COLO 205, HT-29 HCT-116, treated clinically relevant combination therapies, namely 5-FU/oxaliplatin (FO), 5-FU/irinotecan (FI) molecular drugs Cetuximab, Trastuzumab, Vorinostat Everolimus. Treatment results compared originated tumor (Caco-2, DLD-1) co-cultured stromal cells (PBMCs, cancer-associated fibroblasts colorectal origin) directly prepared colon tissues. Different microenvironment compositions altered spheroid patterns. Adding PBMCs increased resistance to FO treatment by 10-15% Caco-2 DLD-1 but decreased FI 16% spheroids. Fibroblast co-cultures 38% had no impact on FO. tissue revealed distinct pattern subgroups not detectable 3D models. The model mimics both characteristics therefore is an invaluable pharmaceutical development.