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Drug Discovery


a tumour, leading to the formation of a hypoxic core. However, spheroids do not typically replicate all the different cancer cell sub-populations includ- ing, importantly, patient-derived cancer stem cells that are required to drive the development of tumour pathology. Spheroids are, therefore, not entirely faithful representations of the pathology of solid tumours, especially as the heterogeneous and disorganised growth associated with tumours is not easy to recapitulate in vitro. An organoid is a simplified tissue model that is


cultured in 3D such that it grows in vitro to form a realistic micro-anatomy, such as that seen within a tumour-derived organoid (Figure 1). They are derived from one or a few cells from a tissue, such as adult stem cells, which can self-organise in cul- ture owing to their self-renewal and differentiation capacities. Importantly, and unlike other models, the cells are never grown in 2D but are seeded and maintained in 3D for the entirety of their culture in


Figure 2


Example images of four different patient-derived


colorectal organoid lines. The


confocal images were captured using a 20x objective on a


CellInsight CX7 High-Content Screening Platform. The organoids are stained for


nuclear (blue) and cytoskeletal (red) markers for imaging. The scale bars represent 50µm


hydrogels. The technique for reliably growing organoids has rapidly improved since the early 2010s and it was named by The Scientist journal as one of the main scientific advancements of 2013. More recently, the journal Nature Methods hailed them as their Method of the Year for 2017. Recent dramatic advances have enabled the long-term growth of organoids to realise their considerable potential as research tools in the laboratory. Consequently, organoids are increasingly being used in both basic research and drug discovery. A key feature of organoids is that they can self-


assemble to preserve the original architecture and function of the solid tumours from which they can be derived. There is accumulating evidence that organoids are likely to be better at predicting effica- cy than conventional cancer cell lines, since they replicate key aspects of solid tumours: genetic diver- sity, differentiation, multicellularity, drug penetra- tion and complex signalling pathway interactions.


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Drug Discovery World Winter 2018/19


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