Prospective derivation of a Living Organoid Biobank of colorectal cancer patients

By M. Wetering, Hayley E. Francies, J. Francis, G. Bounova, F. Iorio, A. Pronk, W. V. Houdt, J. Gorp, A. Taylor-Weiner, L. Kester and 27 more. Cell, 2015

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Summary In Rspondin-based three-dimensional cultures, Lgr5 stem cells from multiple organs form ever-expanding epithelial organoids that retain their tissue identity. Here we report the establishment of tumor organoid cultures from 20 consecutive colorectal carcinoma (CRC) patients. For most, organoids were also generated from adjacent normal tissue. Organoids closely resemble the original tumor. The spectrum of genetic changes within the 'living biobank' agrees well with previous large-scale mutational analyses of CRC. Gene expression analysis indicates that the major CRC molecular subtypes are represented. Tumor organoids are amenable to high-throughput drug screens allowing detection of gene-drug associations. As an example, a single organoid culture was exquisitely sensitive to Wnt secretion (porcupine) inhibitors and carried a mutation in the negative Wnt feedback regulator RNF43, rather than in APC. Organoid technology may fill the gap between cancer genetics and patient trials, complement cell line- and xenograft-based drug studies and allow personalized therapy design.

Subfields: Cancer Research, Hepatology, Oncology

View Paper: https://www.semanticscholar.org/paper/bd4c28577088ceb50a55dd0d0f06abeda27a6802

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In Cancer Research

In Hepatology

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Citations in the corpus

Three-Dimensional in Vitro Cell Culture Models in Drug Discovery and Drug Repositioning (2018, background): “Further, tumoroids that retain tissue identity, paired with organoids of adjacent healthy tissue, can lay the foundation to construct tumor organoid biobanks as repository for drug screening and development (van de Wetering et al., 2015).”
A Living Biobank of Breast Cancer Organoids Captures Disease Heterogeneity. (2018, positive): “The third critical feature of BC organoids is the possibility to perform functional high-throughput drug screens, as demonstrated earlier for CRC organoids (van de Wetering et al., 2015).”
CMScaller: an R package for consensus molecular subtyping of colorectal cancer pre-clinical models (2017, methodology): “GSE35144 28 , GSE64392 16 , GSE74843 15 and E-MTAB-991 14 PDX/organoid microarray gene expression datasets were downloaded from GEO 49 /ArrayExpress 50 and CEL files were pre-processed using the justRMA function in the R package affy 51 , with brainarray Entrez v20 CDFs 52 .”