Drug Discovery


reagents, cells) that are the foundation for developing good preclinical models. How can pharmaceutical companies improve


the drug discovery process for better outcomes? By using more accurate and physiologically-relevant models, pharmaceutical companies can help reduce instances of drug failures further down the line by selecting better drug targets in the early stages.


The necessity of primary cells: study human characteristics not ‘just cells’ Physiologically relevant cell culture models are the mainstay for better understanding and exploring cancer biology. The cell type used, the model creat- ed and the cellular interactions studied all influence the efficiency of early phase drug discovery. While immortalised cell lines are widely used in cancer research, they are overly propagated causing the cells to transform over time and leading to incom-


plete or inaccurate data. Conversely, primary cells are cells isolated directly from human or animal tissue and are becoming increasingly important for studying cancer progression as they better mimic in vivo conditions (Figure 3). Distinguishing between primary cells and generat-


ed cell lines becomes especially relevant when con- sidering a cancer model. Cell lines are typically a cost-effective tool for basic research that can be eas- ily handled and continuously propagated. However, serial passaging is known to cause genotypic and phenotypic variation in cell lines. Variation can often be so far from that of the original tissue to where they do not mimic the in vivo environment very closely. Cells that do not represent the original tissue could result in false negative or false positive findings, leading to increased costs by continuing with ineffective drug substrates or overlooking key targets during the discovery phases. In either case,


Figure 2 Number of papers published using contaminated cell lines by research area. Data courtesy of SPJM Horbach and W Halffman (2017)7


Drug Discovery World Spring 2018


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