Cell line-based platforms to evaluate the therapeutic efficacy of candidate anticancer agents

Key Points Human tumour-derived cell lines have historically had a very important role in the discovery and development of new cancer therapeutics. The National Cancer Institute 60 (NCI60) platform, which introduced the concept of high-throughput cell-based profiling, was crucial not only to the development of technologies that are still being used in various high-throughput discovery platforms, but also to the discovery of several agents that have subsequently been found to demonstrate therapeutic efficacy. Subsequently developed genomic analysis technologies have provided an opportunity to link variable treatment responses to specific underlying genotypes, highlighting the enormous genomic heterogeneity in human cancer and its role in the response to therapy, and revealing the need to reconsider the scale of cell line-based studies to assess the activity of candidate anticancer agents. Consequently, much larger panels of cancer cell lines are beginning to be exploited for the purpose of identifying genomic determinants of drug sensitivity, and several studies have validated the usefulness of this approach to reveal clinically informative biomarkers. This development, together with additional technological developments involving various three-dimensional culture systems and more sophisticated xenograft models, has recently reinvigoratedthe application of cancer cell lines to the analysis of drug efficacy in cancer. Although throughput, as well as the physiological relevance of some of these approaches, remains a limitation of these systems, there seems to be little doubt that tumour-derived cell lines will continue to have a vital role in the preclinical assessment of new candidate anticancer agents. Tumour-derived cell lines are an important model for the discovery and development of new anticancer drugs. The recent development of large panels of cell lines and high-throughput technologies has revitalized this field, and this Review discusses how these tools can be used to screen anticancer agents. Efforts to discover new cancer drugs and predict their clinical activity are limited by the fact that laboratory models to test drug efficacy do not faithfully recapitulate this complex disease. One important model system for evaluating candidate anticancer agents is human tumour-derived cell lines. Although cultured cancer cells can exhibit distinct properties compared with their naturally growing counterparts, recent technologies that facilitate the parallel