Organoids as pure epithelial cultures lack tumor stroma and vasculature. In that respect, PDTX models are more physiologically

relevant and allow drug tests that target host–tumor interactions. Regarding tumor heterogeneity, organoids therefore fall in between purely clonal cancer cell lines and PDTX. Ambivalent is the requirement of matrigel which makes organoid culture more labor intense than culturing cell lines in 2D and adds a complicating parameter to potential drug screens. Then again, the laminin-rich and collagen IV-rich matrigel functions as a basement membrane substitute which, given its tumor origin [39], may be physiologically relevant. Also, organoid culture is considerably easier than maintaining PDTX. Currently available human (cancer) organoid lines are limited to the intestine. However, given recent advances selleck compound in organoid cultures of several mouse tissues (stomach, liver, pancreas, and others [40, 41 and 42]) it seems merely a question of time and effort before equivalent human (cancer) organoids can be cultivated as well. A future collection of organoids that is representative of the respective cancer group, could IDH mutation help patient stratification as well as oncogenic therapeutics. HC is inventor on several patent applications related to organoid culture. Papers of particular interest, published within the period of review, have been highlighted as: • of special

interest We thank Dr. M. van de Wetering for providing organoid pictures. Funding was provided by KWF/PF-Hubr 2007-3956.

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“Current Opinion in Genetics & Development 2014, 24:82–91 This review comes from a themed issue on Cancer genomics Edited by David J Adams and Ultan McDermott For a complete overview see the Issue and the Editorial Available online 26th February 2014 0959-437X/$ – see front Metalloexopeptidase matter, © 2013 The Authors. Published by Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.gde.2013.12.004 Cancer is a disease caused by changes to the DNA, whereby the cancer genome is shaped by the interplay of processes of DNA damage and repair, cellular selection and clonal expansions [1 and 2]. Tumour evolution is classically thought of as a series of clonal expansions that are each triggered by new driver mutations conferring a selective advantage [3 and 4], hence ‘new’ cells undergo Darwinian evolution, very much like how species develop [5 and 6]. Over the past decades, we have learnt much about how cancers develop from studying their genomes, most notably through the introduction of massively parallel sequencing. Comparison of cancer samples from different sites or different time points is increasingly painting a picture of cancers undergoing branching evolution, resulting in competition between different subclones [7, 8, 9, 10, 11, 12 and 13]. In solid tumours, this picture is further complicated by a topological component [8 and 14], with potentially different selection forces operating at different locations of the tumour.