Wojciech Senkowski,Uppsala University, Sweden

Cancer cells grown as two-dimensional (2D) monolayer cell cultures have been widely applied for research in cancer biology and anticancer drug discovery. However, 2D cultures do not closely simulate the complex microenvironment and tissue context of in vivo solid tumors. Using three-dimensional (3D) cell cultures, such as multicellular tumor spheroids (MCTS) has been proposed to address some of these limitations.

Here, I will present the application of MCTS to develop various high-throughput drug-screening (HTS) assays and platforms. This includes viability-based drug screening, large-scale gene expression profiling in MCTS and high-throughput evaluation of drug combinations in 3D. Through application of MCTS for HTS, we were able to identify a number of context-dependent drug responses and candidate molecules that could be further pursued as anticancer drugs. Perhaps most importantly, our work illustrates how 3D cell cultures yield potential to reveal and exploit tumor-specific vulnerabilities and underscores the importance of cell culture conditions in preclinical cancer drug discovery.