Three-dimensional cell culture: the missing link in drug discovery

Cells, grown as monolayers (2D models), are routinely used as initial model systems for evaluating the effectiveness and safety of libraries of molecules with potential as therapeutic drugs. While this initial screening precedes preclinical animal studies before advancing to human clinical trials, cultured cells frequently determine the initial, yet crucial, ‘stop/go’ decisions on the progressing of the development of a drug. Growing cells as three-dimensional (3D) models more analogous to their existence in vivo, for example, akin to a tumour, and possibly co-cultured with other cells and cellular components that naturally occur in their microenvironment may be more clinically relevant. Here, in the context of anti-cancer drug screening, we review 2D and 3D culture approaches, consider the strengths and relevance of each method.

► For anti-cancer drug development, in vitro screening is an early and necessary step.
► We summarise the use and importance, but limitations, of 2D culture for this purpose.
► 3D spheroids better mimic real tumours; particularly if, for example, hypoxia is considered.
► We report on a range of 3D methods, considering strengths and limitations of each.
► Non-partially, we draw attention to examples of commercially available 3D products.