The multicellular tumor spheroid model for high-throughput cancer drug discovery

Introduction: For the past 30 years 2D-cell-based assay models have dominated preclinical cancer drug discovery efforts. 2D-cell-based models fail to predict in vivo efficacy, contributing to a lower success rate and higher cost required to translate an investigational new drug to clinical approval. Technological advances in 3D-cell culture models bridge the gap between 2D and in vivo models to improve upon the current success rates of cancer drug discovery. Areas covered: This review focuses on the multicellular tumor spheroid (MCTS), particularly how this model can be utilized for HTS drug discovery. We discuss the current technologies for uniform culture of MCTS suitable for HTS and detection methods utilized for assay development and drug screening. Expert opinion: Substantial hurdles remain before we reach the ultimate goal of robust HTS of large compound libraries with MCTS models. Specifically, we can group these challenges into three categories: MCTS growth, data collection, and data analysis. The MCTS model should be utilized with fluorescent readouts and high-content imaging with a systems biology approach to model human tumors in vitro. Such models will be more predictive of in vivo efficacy, improving on the current success rates of cancer drug discovery from bench to bedside.