Systems biology: an evolving approach in drug discovery and development.

Investments in systems biology approaches by the pharmaceutical industry have not yet yielded the payoffs envisaged by many. In most cases, a plethora of novel drug targets arising from genomics led to many more failed projects in the pipeline, suggesting that target-based drug discovery may not be an optimal strategy for the industry. Before high-throughput '-omics' technologies and computer analysis became commonplace, most drug candidates were laboriously screened in animal systems to identify compounds that produced useful responses. Interestingly, the targets of many of the compounds that became drugs are still uncertain to this day. It is likely that drugs act on multiple targets in concert over time, the identification of which will require not only system level cataloguing and measurements, but next generation multiscale systems modelling. The concept of a 'differentiated drug response'- elucidating and integrating responses composed of a range of effects on different tissues and, importantly, different time scales - may eventually prove to be the dominant paradigm of systems biology research. In this article, we explore key relevant concepts and technologies that we believe are critical for the future of systems biology and its place in pharmaceutical research.