Prospective derivation of a living organoid biobank of colorectal cancer patients

Cell. 2015 May 7;161(4):933-45. doi: 10.1016/j.cell.2015.03.053.

Abstract

In Rspondin-based 3D cultures, Lgr5 stem cells from multiple organs form ever-expanding epithelial organoids that retain their tissue identity. 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 recapitulate several properties of 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. PAPERCLIP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biological Specimen Banks*
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / pathology*
  • DNA-Binding Proteins / metabolism
  • Drug Screening Assays, Antitumor / methods*
  • Humans
  • Oncogene Proteins / metabolism
  • Organ Culture Techniques
  • Organoids* / drug effects
  • Precision Medicine
  • Ubiquitin-Protein Ligases

Substances

  • DNA-Binding Proteins
  • Oncogene Proteins
  • RNF43 protein, human
  • Ubiquitin-Protein Ligases

Associated data

  • GEO/GSE64392
  • GEO/GSE65253