Drug Discovery


Figure 1 3D Image of a colorectal cancer organoid, courtesy of the National Physical Laboratory. The image was captured with an Airy Beam Light Sheet Microscopy Imaging System of a single fixed colorectal cancer organoid in a hydrogel


are having to compensate for too many failures, which are often weeded out too late in the lengthy development process.


The opportunity for organoids in cancer drug discovery The use of explanted human tumours in drug dis- covery is not new and, as early as the 1950s, vari- ous correlations were claimed between the respons- es of tumours in tissue culture and their subsequent response to cytotoxic chemotherapy1. However, such cultures were variable and not consistently available in the quantities required for routine drug discovery applications. So, these explant cultures were typically used later in drug discovery to con- firm data that had already been generated to select the most promising compounds for further develop- ment. Consequently, such pivotal decisions were often made too late to change the selection of the most promising therapeutic compounds. Immortal


Drug Discovery World Winter 2018/19


cell lines derived from tumours were first developed for scientific research in the 1950s and were used in drug discovery without the variability found with fresh tumour tissue. Although such cell lines often transform over time outside the human body, they represented a significant advance to medical research as, until their introduction, stocks of living cells were limited and took significant effort and time to culture. Since then, numerous other cancer cell lines have been developed but they are typically grown on plastic as flat monolayer cultures. Spheroids can be derived as aggregates from cancer cells or induced pluripotent cells that have been pre- viously grown in monolayers and then assembled into three-dimensional (3D) systems. Spheroids enable cells to communicate with each other as well as their surroundings, providing some similarities to a 3D tumour environment. For example, spheroids can replicate chemical gradients of the various nutrients, oxygen and catabolites found in


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