Advanced cell culture techniques for cancer drug discovery

Abstract

Human cancer cell lines are an integral part of drug discovery practices. However, modeling the complexity of cancer utilizing these cell lines on standard plastic substrata, does not accurately represent the tumor microenvironment. Research into developing advanced tumor cell culture models in a three-dimensional (3D) architecture that more prescisely characterizes the disease state have been undertaken by a number of laboratories around the world. These 3D cell culture models are particularly beneficial for investigating mechanistic processes and drug resistance in tumor cells. In addition, a range of molecular mechanisms deconstructed by studying cancer cells in 3D models suggest that tumor cells cultured in two-dimensional monolayer conditions do not respond to cancer therapeutics/compounds in a similar manner. Recent studies have demonstrated the potential of utilizing 3D cell culture models in drug discovery programs; however, it is evident that further research is required for the development of more complex models that incorporate the majority of the cellular and physical properties of a tumor.

Figure 1

Phenotypic properties of a panel of breast cancer cell lines cultured in two-dimensional (2D) and three-dimensional (3D) cell culture systems. Brightfield (BF) and immunofluorescence (IF; central Z-slice through a spheroid) microscopy illustrate 2D cell cultures and 3D structures unique to each cell line. MDA-MB-231 in 2D (A) and 3D (A’, A’’), MCF-7 in 2D (B) and 3D (B’, B’’) and BT-474 in 2D (C) and 3D (C’, C’’). Scale bar = 50 μm.

Figure 2

Advantages of incorporating elements of the tumor microenvironment in drug discovery programmes.