With low success rates in clinical trials, drug discovery remains a slow and costly business. Currently, more than half of all drugs fail in Phase II and Phase III clinical trials due to a lack of efficacy and about another third of drugs fail due to safety issues including an insufficient therapeutic index. The importance of the extracellular matrix (ECM) in cell behavior, it is now well-accepted that culturing cells in three-dimensional (3D) systems that mimic key factors of tissue is much more representative of the in vivo environment than simple two-dimensional (2D) monolayers.
“Currently, the majority of cell-based HTS is being carried out on cultured cells propagated in two-dimensions (2D) on plastic surfaces optimized for tissue culture. At the same time, compelling evidence suggests that cells cultured in these non-physiological conditions are not representative of cells residing in the complex microenvironment of a tissue. This discrepancy is thought to be a significant contributor to the high failure rate in drug discovery, where only a low percentage of drugs investigated ever make it through the gamut of testing and approval to the market. Thus, three-dimensional (3D) cell culture technologies that more closely resemble in vivo cell environments are now being pursued with intensity as they are expected to accommodate better precision in drug discovery.”
In this review, Sigrid A Langhans provides an overview on the most common 3D cell culture techniques, address the opportunities they provide for both drug repurposing and the discovery of new drugs, and discuss the challenges in moving those techniques into mainstream drug discovery.